Submitted:
19 August 2025
Posted:
19 August 2025
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Preprints on COVID-19 and SARS-CoV-2
Abstract
With the advent of Covid-19, it is necessary to repurpose new treatment alternatives, either in the form of an effective single dose of these antidiabetic drug agents or an efficacious combination of them for elderly population with or had suffered this condition. Such new treatment alternatives would prevent the development of the common comorbidities, such as heart failure, nephropathy, neuropathy and retinopathy. This mini-review has the objective of predicting the targets of bioactive small molecules in human using healthcare applied artificial intelligence. Method. The tool is a tuned algorithm, with novel data in web interface. Results. Information figures of Swiss Target Prediction, which allow predictions on therapy combinations and probable side effects, were reordered. This tool is useful to understand the molecular mechanisms underlying a given phenotype or bioactivity, to rationalize possible favorable or unfavorable side effects, to predict off-targets of known molecules and to clear the way to drug repurposing. Predictions are done using a ligand-based approach, based on the similarity between a query molecule and the known ligands of a large collection of protein targets. Conclusion. The result of this study highlighted crucial recommendations for the use of some of the antidiabetic agent groups in diabetic patients, which would also reduce the cost of their therapies. This is very important for patients who, due to their ill condition, are obliged to take medicine for a long period and whose life depends on it.
Keywords:
Antidiabetic drugs
; Artificial intelligence
; COVID-19
; Diabetes
; Drug targets
Introduction
Diabetes is a chronic metabolic disease with high magnitude of morbidity and mortality, which heralds it as one of the biggest problems of public health concern in the world. The number of people with diabetes and pre-diabetes is growing exponentially. Due to its high and increasing incidence, the associated healthcare costs, and threatening medical complications, it is considered as one of the priority non-communicable diseases [1]. The prevalence of type 2 diabetes mellitus (T2DM) is internationally ever-growing (Figure 1).
Therefore, prevention, diagnosis and control of insulin resistance and T2DM are of increasing importance [2]. It is pertinent to design a proper multifactorial management of patients with type 2 diabetes that aims at controlling blood pressure, hyperglycemia and dyslipidemia by using both lifestyle changes (reduction of sodium and fat intake, regular physical activity, weight loss in overweight patients, smoking cessation) and drug therapy [3].
Glycemia and insulin resistance are important regulators of multiple physiological processes and their dysregulation has wide-ranging consequences. During treatment, the patients may undergo rapid changes in their condition or suffer diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar status (HHS) [4]. A strict glycemic control based on the maintenance of fasting plasma glucose (FPG) at between 4.4-6.1 mmol/L and 2-hour postprandial plasma glucose (2 h PG) at 6.1-7.8 mmol/L) should be instituted. For the common type patients, FPG should be between 6.1 and 7.8 mmol/L and 2 h PG, between 7.8 and10.0 mmol/L.
Diabetes During Covid Time
The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a notable challenge for diabetic patients. People with diabetes have a higher risk of developing different infectious diseases; and hence, increased mortality rate [5]. Diabetic patients who suffered from coronavirus disease 2019 (COVID-19) experienced higher mortality and higher proportion of critically ill condition [6], as opposed to non-diabetic infected patients. This difference in severity may be associated to the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. In addition, age, environmental conditions, socioeconomic status, comorbidities and interventional timing increase the risks for severe infection, morbidity and mortality in these patients [7]. Elderly people and patients with comorbidities suffer severe coronavirus disease.
Patients with hipoglycemic, hypolipidemic and antiatherogenic effects, the prevalence of diabetes and obesity, as well as high human development index, and location at < 500 or > 2000 above sea level were associated with higher mortality rate in COVID-19 disease [8]. Therefore, diabetes and hypertension are the main cause of adult mortality worldwide, due more than 70% of adult population living in areas with high social marginality suffer diabetes, hypertension and obesity [9], respect clinical data.
Effect of Nutritional State
In fact, malnutrition is a common event among severe patients, such as elderly adults and patients with comorbidity that suffered coronavirus disease 2019 (COVID-19). The controlling nutritional status (CONUT) score, which comprises serum albumin level, cholesterol level and lymphocytes count, as well as a combined CONUT-lactate dehydrogenase-C-reactive protein score expressed a predictive capacity even superior to that of NRS-2002 (0.81% and 0.92% vs. 0.79%) in midlife and elder COVID-19 patients [10]. This author suggests that older males with severe inflammation, gastrointestinal symptoms and pre-existing comorbidities (diabetes, obesity or hypertension) are more prone to malnutrition and subsequently poor COVID-19 prognosis, both during the acute phase and during convalescence. Also, the epidemic of diabetes and dementia are more in older adults. The risk for dementia appears to increase in patients with diabetes, and patients with both dementia and diabetes appear to be at greater risk for severe hypoglycemia [11].
Significant endothelial cell loss has been reported in long-term disease and in cases of poor metabolic control, and corneal thickness may increase in diabetic patients [12], and as the prevalence of malnutrition is high in patients with cancer, and systematic screening for its treatment of malnutrition is necessary. The prevalence of malnutrition by disease site is as follows: head and neck, 48.9%; leukemia/lymphoma, 34.0%; lung, 45.3%; colon/rectum, 39.3%; esophagus and/or stomach, 60.2%; pancreas, 66.7%; breast, 20.5%; ovaries/uterus, 44.8%; and prostate, 13.9%. [13], and cancer is the main disorder in old patients.
Diabetes and Hypertension
The association between diabetes mellitus and hypertension has been described in 60 to 65% of diabetics, and hypertension is two to three times more common among diabetics compared with non-diabetics [14]. Aging process induces changes in renal physiology such as glomerular filtration rate reduction, and alteration in water and electrolytes handling [15], making the old person frail, and finding association between cardiovascular disorders and falls in older adults. Indeed, several cardiovascular disorders, including stroke, coronary artery disease, valvular heart disease, arterial stiffness, arrhythmia, orthostatic hypotension, and carotid sinus hypersensitivity, were consistently associated with falls [16], heart failure prevalence will more than 10% of persons over the age of 70 years in an age-dependent manner. The prevalence is up to 74% in older individuals over the age of 80 years or those over 70 years old with a high burden of comorbidities and chronic diseases [17].
On the other hand, chronic overconsumption of animal fats causes diabetes mellitus and obesity. The underlying molecular mechanisms encompass leptin resistance, a decrease in rewarding effects of physical activities, xanthine oxidase-induced oxidative stress in vasculature and peripheral tissue, impaired activation of incretin signaling and deviation in food preference [18]. Hyperuricemia can lead to cardiovascular and renal complications in patients with diabetes [19].
High-fat feeding and hyperglycemia, key risk factors for the development of metabolic syndrome (MetS), are being increasingly associated with higher risk of developing dementia and cognitive decline. Despite the effect of high fat-feeding and hyperglycemia on the levels of systemic inflammatory cytokines, gliosis in the hippocampus and immune infiltration in cerebral hemispheric tissue [20], hyperglycemia alone preferentially induces an increase in microglial numbers and astrocytosis in the hippocampus. In addition, it is associated with the peripheral recruitment of leukocytes to the cerebrovasculature, but not with systemic inflammation.
Changes in glucose levels induce neuroendocrine response, which works to prevent or correct glycemia. The main area of the brain that regulates glycemic homeostasis is the hypothalamus; consequently, metabolic diseases such as obesity and diabetes are related to imbalance of this control [21,22]. The multi-resultant effects of this imbalance are the induction of oxidative damage, production of hyperglycemia, heart failure, increased brain oxidative stress, impaired brain mitochondrial function, increased brain apoptosis, increased tau protein expression, increased phosphorylation of tau protein expression and amyloid beta levels, and decreased dendritic spine density [23]. Free radicals are normally generated in many cellular metabolic pathways as reactive oxygen species (ROS), or Nitrogen Oxygen Species (NOS). These radicals may interact with various cellular components and induce cell injury. Oxidative stress results when there is a serious imbalance between generation of free radicals and the antioxidant capacity, or disturbance of glutathione homeostasis in the body. When free radicals exceed the antioxidant capacity, cell injury causes diverse physiological and pathologic changes, including the presence of clinical disorders [24], in elderly.
Antidiabetic Drugs
Antidiabetic drugs allow the optimization of diabetes treatment and provide opportunities to improve the management of the disease (a condition that can be treated and controlled, but has no cure yet). In addition, these drugs can reduce the complications associated with this disorder. Currently, the main groups of antidiabetic agents include:
- Alpha-glucosidase inhibitors (acarbose, miglitol) [25].
- Dipeptidyl peptidase 4 (DPP-4) inhibitors (alogliptan, linagliptan, saxagliptin, sitagliptin) [26].
- Meglitinides (nateglinide, repaglinide) [27].
- Non-sulfonylureas (metformin) [28].
- Sulfonylureas (glimepiride, glipizide, glyburide, tolazamide, tolbutamide, gliclazide) [31].
- Thiazolidinediones (rosiglitazone, pioglitazone) [32].
Type 2 diabetes pharmacotherapy with a single agent does not generally provide durable glycemic control. Hence, the mainstay choice is to add a second-line or third-line agents once unfavorable side effects appear or when glycemic control with monotherapy deteriorates. In fact, polypharmacy and less malnutrition problems improve the health and well-being of older adults.
Predicting the Targets of Antidiabetic Agents
With artificial intelligence applications in healthcare at predicting the targets of antidiabetic agents in human, we used the tool of a tuned algorithm, with novel data in web interface. This study used figures to reorder the information of Swiss Target Prediction that allow predictions on combination therapy and probable side effects. This tool helps to understand the molecular mechanisms underlying a given phenotype or bioactivity, rationalize possible favorable or unfavorable side effects, predict off-targets of known molecules and clear the way to drug repurposing.
Predictions are done using a ligand-based approach, which considers the similarity between a query molecule and the known ligands of a large collection of protein targets as explained below (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, Table 20 and Table 21).
Group 1. Alpha-glucosidase inhibitors (AGIs) and Target Predictions with Artificial Intelligence. The AGIs are ligand-based inhibitors whose mechanism of actions is to halt, in small intestine, the absorption of carbohydrates. AGIs perform this function by inhibiting enzymes, such as glucoamylase, sucrase, maltase and isomaltase that convert complex non-absorbable carbohydrates into simple absorbable carbohydrates; thus, halting the absorption of elements. Currently, there are two know available AGIs with 80% main target prediction.
 |
Table 1.
Acarbosa.
| Target | Target Class | Probability* |
| Pancreatic alpha-amylase | Hydrolase | 0.844359912 |
| AMY1C | Enzyme | 0.767817837 |
| Lysosomal alpha-glucosidase | Hydrolase | 0.767817837 |
| Sucrase-isomaltase | Enzyme | 0.369201611 |
| Maltase-glucoamylase | Hydrolase | 0.264198975 |
| Trehalase | Enzyme | 0.084065592 |
| Cyclin-dependent kinase 1 | Kinase | 0.074564954 |
| Carbonic anhydrase II | Lyase | 0.074564954 |
| Carbonic anhydrase I | Lyase | 0.074564954 |
| Carbonic anhydrase XII | Lyase | 0.074564954 |
| Carbonic anhydrase IX | Lyase | 0.074564954 |
 |
Table 2.
Miglitol.
| Target | Target Class | Probability* |
| Maltase-glucoamylase | Hydrolase | 1 |
| Lysosomal alpha-glucosidase | Hydrolase | 1 |
| Sucrase-isomaltase | Enzyme | 1 |
| Alpha-L-fucosidase I | Enzyme | 0.440152276 |
| Beta-glucocerebrosidase | Enzyme | 0.409951926 |
| Neutral alpha-glucosidase AB | Enzyme | 0.389384066 |
| Alpha-galactosidase A | Enzyme | 0.369032376 |
| Alpha-L-fucosidase 2 | Enzyme | 0.369032376 |
| Ceramide glucosyltransferase | Transferase | 0.337981759 |
| Beta-glucosidase | Enzyme | 0.328089366 |
| Neutral alpha-glucosidase C | Enzyme | 0.287108994 |
| Beta-galactosidase | Hydrolase | 0.225492374 |
| Beta-mannosidase (by homology) | Enzyme | 0.061914931 |
| Liver glycogen phosphorylase | Enzyme | 0.061914931 |
| Glycogen debranching enzyme | Enzyme | 0.051713312 |
| Lysosomal alpha-mannosidase | Enzyme | 0.051713312 |
| Lanosterol synthase | Enzyme | 0.041470299 |
| Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase | Enzyme | 0.031226558 |
| Vesicular acetylcholine transporter | Electrochemical transporter | 0.031226558 |
| Phospholipase A2 group IIA | Enzyme | 0.031226558 |
| Phospholipase A2 group 1B | Enzyme | 0.031226558 |
| Polyadenylate-binding protein 1 | Unclassified protein | 0.031226558 |
Group 2. Dipeptidyl peptidase 4 inhibitors (DPP-49) and Target Predictions with Artificial Intelligence. DPP-4 inhibitors: These substances inhibit DPP-4 activity in peripheral plasma. In the peripheral circulations, DPP-4 inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), that stimulates insulins secretion. Therefore, these inhibitors prevent this inactivation, and thereby, makes it possible the GLP-1 stimulation of insulin secretion. Presently, there are four available antidiabetic DPP-4 inhibitor agents with 66.7% to 80% main target prediction.
 |
Table 3.
Alogliptin Benzoate.
| Target | Target Class | Probability* |
| Dipeptidyl peptidase IV | Protease | 1 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.097239989 |
| Dipeptidyl peptidase VIII | Protease | 0.097239989 |
| Cyclin-dependent kinase 4/cyclin D1 | Kinase | 0.097239989 |
| Cyclin-dependent kinase 2/cyclin E | Other cytosolic protein | 0.097239989 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.097239989 |
| Protein kinase C theta | Kinase | 0.097239989 |
| Acetylcholine receptor; alpha1/beta1/delta/gamma | Ligand-gated ion channel | 0.097239989 |
| Neuronal acetylcholine receptor; alpha3/beta4 | Ligand-gated ion channel | 0.097239989 |
| Protein kinase C delta | Kinase | 0.097239989 |
| Protein kinase C alpha | Kinase | 0.097239989 |
| Delta opioid receptor | Family A G protein-coupled receptor | 0.097239989 |
| Dipeptidyl peptidase II | Protease | 0.097239989 |
| Serotonin 1f (5-HT1f) receptor | Family A G protein-coupled receptor | 0.097239989 |
| Serotonin 1b (5-HT1b) receptor | Family A G protein-coupled receptor | 0.097239989 |
| Serotonin 1d (5-HT1d) receptor | Family A G protein-coupled receptor | 0.097239989 |
| Mu opioid receptor | Family A G protein-coupled receptor | 0.097239989 |
| Serotonin 5a (5-HT5a) receptor (by homology) | Family A G protein-coupled receptor | 0.097239989 |
| Bromodomain-containing protein 4 | Reader | 0.097239989 |
| Muscarinic acetylcholine receptor M2 (by homology) | Family A G protein-coupled receptor | 0.097239989 |
| Poly [ADP-ribose] polymerase 3 | Enzyme | 0.097239989 |
| Protein kinase C epsilon | Kinase | 0.097239989 |
| Protein kinase C eta | Kinase | 0.097239989 |
| PDZ-binding kinase | Kinase | 0.097239989 |
| Caspase-3 | Protease | 0.097239989 |
| Caspase-7 | Protease | 0.097239989 |
| Serine/threonine-protein kinase AKT | Kinase | 0.097239989 |
| Serine/threonine-protein kinase AKT | Kinase | 0.097239989 |
| Kinesin-like protein 1 | Other cytosolic protein | 0.097239989 |
| Dipeptidyl peptidase IX | Protease | 0.097239989 |
| Neurokinin 1 receptor (by homology) | Family A G protein-coupled receptor | 0.097239989 |
| Retinoid X receptor alpha | Nuclear receptor | 0.097239989 |
| Norepinephrine transporter | Electrochemical transporter | 0.097239989 |
| Serotonin transporter | Electrochemical transporter | 0.097239989 |
| Serine/threonine-protein kinase PIM2 | Kinase | 0.097239989 |
| Serine/threonine-protein kinase WEE1 | Kinase | 0.097239989 |
| Dopamine transporter | Electrochemical transporter | 0.097239989 |
| Trace amine-associated receptor 1 (by homology) | Family A G protein-coupled receptor | 0.097239989 |
| Tyrosyl-DNA phosphodiesterase 1 | Enzyme | 0.097239989 |
| Dual specificity protein kinase TTK | Kinase | 0.097239989 |
| Poly [ADP-ribose] polymerase 2 | Enzyme | 0.097239989 |
| Serotonin 3a (5-HT3a) receptor | Ligand-gated ion channel | 0.097239989 |
| Rho-associated protein kinase 2 | Kinase | 0.097239989 |
| Inhibitor of apoptosis protein 3 | Other cytosolic protein | 0.097239989 |
| CaM kinase II | Kinase | 0.097239989 |
| Protein farnesyltransferase | Enzyme | 0.097239989 |
| Complement factor D | Protease | 0.097239989 |
| Cyclin-dependent kinase 1 | Kinase | 0.097239989 |
| Serotonin 4 (5-HT4) receptor | Family A G protein-coupled receptor | 0.097239989 |
| Dopamine D1 receptor | Family A G protein-coupled receptor | 0.097239989 |
| GABA-A receptor; alpha-1/beta-2/gamma-2 | Ligand-gated ion channel | 0.097239989 |
| Maternal embryonic leucine zipper kinase | Kinase | 0.097239989 |
| CDK2/Cyclin A | Kinase | 0.097239989 |
| Protein kinase C beta | Kinase | 0.097239989 |
| Ribosomal protein S6 kinase alpha 2 | Kinase | 0.097239989 |
| Inhibitor of nuclear factor kappa B kinase beta subunit | Kinase | 0.097239989 |
| Serotonin 1e (5-HT1e) receptor | Family A G protein-coupled receptor | 0.097239989 |
| Cyclooxygenase-1 | Oxidoreductase | 0.097239989 |
| C-C chemokine receptor type 2 | Family A G protein-coupled receptor | 0.097239989 |
| Melanocortin receptor 4 | Family A G protein-coupled receptor | 0.097239989 |
| Transient receptor potential cation channel subfamily M member 8 | Voltage-gated ion channel | 0.097239989 |
| Tyrosine-protein kinase ABL | Kinase | 0.097239989 |
| Dopamine D5 receptor | Family A G protein-coupled receptor | 0.097239989 |
| Dopamine D4 receptor | Family A G protein-coupled receptor | 0.097239989 |
| Phosphodiesterase 4D | Phosphodiesterase | 0.097239989 |
| Mucosa-associated lymphoid tissue lymphoma translocation protein 1 | Hydrolase | 0.097239989 |
| Tyrosine-protein kinase receptor UFO | Kinase | 0.097239989 |
| Proto-oncogene tyrosine-protein kinase MER | Kinase | 0.097239989 |
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | Voltage-gated ion channel | 0.097239989 |
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 | Voltage-gated ion channel | 0.097239989 |
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 | Voltage-gated ion channel | 0.097239989 |
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 | Voltage-gated ion channel | 0.097239989 |
| Probable G-protein coupled receptor 142 | Family A G protein-coupled receptor | 0.097239989 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.097239989 |
| Dipeptidyl peptidase I | Protease | 0.097239989 |
| Renin | Protease | 0.097239989 |
| WD repeat-containing protein 5 | Unclassified protein | 0.097239989 |
| CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) | Kinase | 0.097239989 |
| Kappa Opioid receptor | Family A G protein-coupled receptor | 0.097239989 |
| Sigma opioid receptor | Membrane receptor | 0.097239989 |
| Cyclin-dependent kinase 9 | Kinase | 0.097239989 |
| Urokinase-type plasminogen activator | Protease | 0.097239989 |
| Tyrosine-protein kinase receptor TYRO3 | Kinase | 0.097239989 |
| Baculoviral IAP repeat-containing protein 2 | Enzyme | 0.097239989 |
| Cyclin-dependent kinase 2 | Kinase | 0.097239989 |
| Cyclin-dependent kinase 4 | Kinase | 0.097239989 |
| Amine oxidase, copper containing | Enzyme | 0.097239989 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.097239989 |
| Tyrosine-protein kinase receptor FLT3 | Kinase | 0.097239989 |
| Peptide N-myristoyltransferase 1 | Enzyme | 0.097239989 |
| Protein kinase N2 | Kinase | 0.097239989 |
| Prolyl endopeptidase | Protease | 0.097239989 |
| Rho-associated protein kinase 1 | Kinase | 0.097239989 |
| DNA-directed RNA polymerase I subunit RPA1 | Enzyme | 0.097239989 |
| Cell division control protein 42 homolog | Unclassified protein | 0.097239989 |
| Peregrin | Reader | 0.097239989 |
| Butyrylcholinesterase | Hydrolase | 0.097239989 |
| Dual specificity phosphatase Cdc25C | Phosphatase | 0.097239989 |
| Cathepsin S | Protease | 0.097239989 |
| Cathepsin G | Protease | 0.097239989 |
 |
Table 4.
Linagliptin.
| Target | Target Class | Probability* |
| Muscarinic acetylcholine receptor M1 | Family A G protein-coupled receptor | 1 |
| Dipeptidyl peptidase IV | Protease | 1 |
| Fibroblast activation protein alpha | Protease | 1 |
| Cyclin-dependent kinase 4 | Kinase | 0.110612204 |
| Dipeptidyl peptidase IX | Protease | 0.110612204 |
| MAP kinase p38 alpha | Kinase | 0.110612204 |
| C-C chemokine receptor type 8 | Family A G protein-coupled receptor | 0.110612204 |
| Tyrosine-protein kinase ABL | Kinase | 0.110612204 |
| Platelet-derived growth factor receptor beta | Kinase | 0.110612204 |
| Thrombin and coagulation factor X | Protease | 0.110612204 |
| Melanin-concentrating hormone receptor 1 | Family A G protein-coupled receptor | 0.110612204 |
| Gonadotropin-releasing hormone receptor | Family A G protein-coupled receptor | 0.110612204 |
| Cyclin-dependent kinase 6 | Kinase | 0.110612204 |
| Phosphoenolpyruvate carboxykinase cytosolic | Enzyme | 0.110612204 |
| Neuropeptide Y receptor type 1 | Family A G protein-coupled receptor | 0.110612204 |
| Protein Mdm4 | Unclassified protein | 0.110612204 |
| Bradykinin B2 receptor | Family A G protein-coupled receptor | 0.110612204 |
| Bradykinin B1 receptor | Family A G protein-coupled receptor | 0.110612204 |
| p53-binding protein Mdm-2 | Other nuclear protein | 0.110612204 |
| Thrombin | Protease | 0.110612204 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.110612204 |
| Serine/threonine-protein kinase PIM2 | Kinase | 0.110612204 |
| Serine/threonine-protein kinase PIM3 | Kinase | 0.110612204 |
| Leukocyte elastase | Protease | 0.110612204 |
| Trypsin I | Protease | 0.110612204 |
| NAD-dependent deacetylase sirtuin 1 | Eraser | 0.110612204 |
| Receptor protein-tyrosine kinase erbB-2 | Kinase | 0.110612204 |
| Insulin-like growth factor I receptor | Kinase | 0.110612204 |
| Serine/threonine-protein kinase AKT | Kinase | 0.110612204 |
| Bromodomain-containing protein 4 | Reader | 0.110612204 |
| Vasopressin V1b receptor | Family A G protein-coupled receptor | 0.110612204 |
| Cat eye syndrome critical region protein 2 | Reader | 0.110612204 |
| Bromodomain-containing protein 9 | Reader | 0.110612204 |
| Sonic hedgehog protein (by homology) | Unclassified protein | 0.110612204 |
| CREB-binding protein/p53 | Writer | 0.110612204 |
| Matrix metalloproteinase 1 | Protease | 0.110612204 |
| Somatostatin receptor 5 | Family A G protein-coupled receptor | 0.110612204 |
| Somatostatin receptor 3 | Family A G protein-coupled receptor | 0.110612204 |
| C-C chemokine receptor type 4 | Family A G protein-coupled receptor | 0.110612204 |
| Tryptase beta-1 | Protease | 0.110612204 |
| Insulin receptor | Kinase | 0.110612204 |
| ALK tyrosine kinase receptor | Kinase | 0.110612204 |
| Beta-secretase 1 | Protease | 0.110612204 |
| Mitogen-activated protein kinase kinase kinase 8 | Kinase | 0.110612204 |
| EZH2/SUZ12/EED/RBBP7/RBBP4 | Writer | 0.110612204 |
| Cyclin-dependent kinase 2 | Kinase | 0.110612204 |
| Cyclin-dependent kinase 1 | Kinase | 0.110612204 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.110612204 |
| MAP kinase signal-integrating kinase 2 | Kinase | 0.110612204 |
| MAP kinase-interacting serine/threonine-protein kinase MNK1 | Kinase | 0.110612204 |
| Tyrosine-protein kinase receptor FLT3 | Kinase | 0.110612204 |
| Arachidonate 12-lipoxygenase | Enzyme | 0.110612204 |
| Hepatocyte growth factor receptor | Kinase | 0.110612204 |
| Tyrosine-protein kinase receptor TYRO3 | Kinase | 0.110612204 |
| Cyclin-dependent kinase 2/cyclin E1 | Kinase | 0.110612204 |
| Estrogen receptor alpha | Nuclear receptor | 0.110612204 |
| Adenosylhomocysteinase | Enzyme | 0.110612204 |
| Cyclin T1 | Other cytosolic protein | 0.110612204 |
| Tyrosine-protein kinase ITK/TSK | Kinase | 0.110612204 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.110612204 |
| Smoothened homolog | Frizzled family G protein-coupled receptor | 0.110612204 |
| Mu opioid receptor | Family A G protein-coupled receptor | 0.110612204 |
| Delta opioid receptor | Family A G protein-coupled receptor | 0.110612204 |
| Microtubule-associated protein 2 | Unclassified protein | 0.110612204 |
| Methionine aminopeptidase 1 | Protease | 0.110612204 |
| Rho-associated protein kinase 2 | Kinase | 0.110612204 |
| Dual specificity tyrosine-phosphorylation-regulated kinase 1B | Kinase | 0.110612204 |
| ATPase family AAA domain-containing protein 2 | Reader | 0.110612204 |
| Platelet activating factor receptor | Family A G protein-coupled receptor | 0.110612204 |
| Cyclin-dependent kinase 9 | Kinase | 0.110612204 |
| Protein kinase C mu | Kinase | 0.110612204 |
| Ketohexokinase | Enzyme | 0.110612204 |
| Tyrosine-protein kinase FYN | Kinase | 0.110612204 |
| Tyrosine-protein kinase BLK | Kinase | 0.110612204 |
| Receptor protein-tyrosine kinase erbB-4 | Kinase | 0.110612204 |
| Tyrosine-protein kinase BMX | Kinase | 0.110612204 |
| Sodium/calcium exchanger 1 | Electrochemical transporter | 0.110612204 |
| Ephrin type-A receptor 8 | Kinase | 0.110612204 |
| Tyrosine-protein kinase FRK | Kinase | 0.110612204 |
| Ephrin type-B receptor 3 | Kinase | 0.110612204 |
| Dipeptidyl peptidase VIII | Protease | 0.110612204 |
| Serine/threonine-protein kinase AKT2 | Kinase | 0.110612204 |
| Melanocortin receptor 4 | Family A G protein-coupled receptor | 0.110612204 |
| Sigma opioid receptor | Membrane receptor | 0.110612204 |
| Serotonin 1b (5-HT1b) receptor | Family A G protein-coupled receptor | 0.110612204 |
| Serotonin 1d (5-HT1d) receptor | Family A G protein-coupled receptor | 0.110612204 |
| Platelet-derived growth factor receptor alpha | Kinase | 0.110612204 |
| Dopamine D1 receptor | Family A G protein-coupled receptor | 0.110612204 |
| TGF-beta receptor type I | Kinase | 0.110612204 |
| Receptor-interacting serine/threonine-protein kinase 3 | Enzyme | 0.110612204 |
| Vascular endothelial growth factor receptor 1 | Kinase | 0.110612204 |
| Vascular endothelial growth factor receptor 3 | Kinase | 0.110612204 |
| Fibroblast growth factor receptor 1 | Kinase | 0.110612204 |
| Transitional endoplasmic reticulum ATPase | Primary active transporter | 0.110612204 |
| Heat shock protein HSP 90-alpha | Other cytosolic protein | 0.110612204 |
| Inhibitor of apoptosis protein 3 | Other cytosolic protein | 0.110612204 |
| Baculoviral IAP repeat-containing protein 2 | Enzyme | 0.110612204 |
| Vasopressin V2 receptor (by homology) | Family A G protein-coupled receptor | 0.110612204 |
| Oxytocin receptor (by homology) | Family A G protein-coupled receptor | 0.110612204 |
| MAP kinase-activated protein kinase 2 | Kinase | 0.110612204 |
 |
Table 5.
Saxagliptin.
| Target | Target Class | Probability* |
| Dipeptidyl peptidase IV | Protease | 0.968095103 |
| Dipeptidyl peptidase VIII | Protease | 0.959682015 |
| Dipeptidyl peptidase IX | Protease | 0.959682015 |
| Fibroblast activation protein alpha | Protease | 0.126610169 |
| Dipeptidyl peptidase II | Protease | 0.10994577 |
| 11-beta-hydroxysteroid dehydrogenase 1 | Enzyme | 0.101613855 |
| Norepinephrine transporter | Electrochemical transporter | 0.101613855 |
| Serotonin transporter | Electrochemical transporter | 0.101613855 |
| Androgen Receptor | Nuclear receptor | 0.101613855 |
| 11-beta-hydroxysteroid dehydrogenase 2 | Enzyme | 0.101613855 |
| Lysine-specific histone demethylase 1 | Eraser | 0.101613855 |
| Transient receptor potential cation channel subfamily V member 3 | Voltage-gated ion channel | 0.101613855 |
| Delta opioid receptor | Family A G protein-coupled receptor | 0.101613855 |
| Prolyl endopeptidase | Protease | 0.101613855 |
| Mu opioid receptor (by homology) | Family A G protein-coupled receptor | 0.101613855 |
| Insulin-like growth factor I receptor | Kinase | 0.101613855 |
| Dopamine D1 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Alpha-1a adrenergic receptor (by homology) | Family A G protein-coupled receptor | 0.101613855 |
| S-methyl-5-thioadenosine phosphorylase | Enzyme | 0.101613855 |
| Serotonin 2b (5-HT2b) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Alpha-2a adrenergic receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin 1b (5-HT1b) receptor (by homology) | Family A G protein-coupled receptor | 0.101613855 |
| Alpha-2b adrenergic receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin 2a (5-HT2a) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin 2c (5-HT2c) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin 6 (5-HT6) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.101613855 |
| Cytochrome P450 2D6 | Cytochrome P450 | 0.101613855 |
| Serine/threonine-protein kinase PIM2 | Kinase | 0.101613855 |
| Serine/threonine-protein kinase PIM3 | Kinase | 0.101613855 |
| C-C chemokine receptor type 1 | Family A G protein-coupled receptor | 0.101613855 |
| Glutamate NMDA receptor; GRIN1/GRIN2B | Ligand-gated ion channel | 0.101613855 |
| Nociceptin receptor | Family A G protein-coupled receptor | 0.101613855 |
| Beta-1 adrenergic receptor | Family A G protein-coupled receptor | 0.101613855 |
| Beta-3 adrenergic receptor | Family A G protein-coupled receptor | 0.101613855 |
| Glutamate [NMDA] receptor subunit epsilon 2 | Ligand-gated ion channel | 0.101613855 |
| Glycine transporter 1 | Electrochemical transporter | 0.101613855 |
| Cathepsin S | Protease | 0.101613855 |
| Dipeptidyl peptidase I | Protease | 0.101613855 |
| Renin | Protease | 0.101613855 |
| Serotonin 7 (5-HT7) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Cytochrome P450 19A1 | Cytochrome P450 | 0.101613855 |
| Somatostatin receptor 3 | Family A G protein-coupled receptor | 0.101613855 |
| Adrenergic receptor beta | Family A G protein-coupled receptor | 0.101613855 |
| Protein kinase C theta | Kinase | 0.101613855 |
| Heat shock protein HSP 90-alpha | Other cytosolic protein | 0.101613855 |
| Neurokinin 1 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin 1d (5-HT1d) receptor | Family A G protein-coupled receptor | 0.101613855 |
| Thrombin and coagulation factor X | Protease | 0.101613855 |
| Squalene synthetase (by homology) | Enzyme | 0.101613855 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.101613855 |
| Urotensin II receptor | Family A G protein-coupled receptor | 0.101613855 |
| Cytochrome P450 51 | Cytochrome P450 | 0.101613855 |
| P-glycoprotein 1 | Primary active transporter | 0.101613855 |
| Cathepsin K | Protease | 0.101613855 |
| Neuronal acetylcholine receptor; alpha3/alpha6/beta2/beta3 | Ligand-gated ion channel | 0.101613855 |
| Egl nine homolog 1 | Oxidoreductase | 0.101613855 |
| Sodium channel protein type V alpha subunit | Voltage-gated ion channel | 0.101613855 |
| Dopamine D5 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Cyclin-dependent kinase 4/cyclin D1 | Kinase | 0.101613855 |
| Cyclin-dependent kinase 2/cyclin E | Other cytosolic protein | 0.101613855 |
| Calcium sensing receptor | Family C G protein-coupled receptor | 0.101613855 |
| Steryl-sulfatase | Enzyme | 0.101613855 |
| Prostanoid EP2 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Prostanoid EP3 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Peptide N-myristoyltransferase 1 | Enzyme | 0.101613855 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.101613855 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.101613855 |
| Histamine H4 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serine/threonine-protein kinase ILK-1 | Kinase | 0.101613855 |
| CaM kinase II | Kinase | 0.101613855 |
| Protein kinase C alpha | Kinase | 0.101613855 |
| Voltage-gated potassium channel subunit Kv1.5 | Voltage-gated ion channel | 0.101613855 |
| Synaptic vesicular amine transporter (by homology) | Electrochemical transporter | 0.101613855 |
| Histamine H1 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Muscarinic acetylcholine receptor M5 | Family A G protein-coupled receptor | 0.101613855 |
| Alpha-1d adrenergic receptor | Family A G protein-coupled receptor | 0.101613855 |
| Muscarinic acetylcholine receptor M3 | Family A G protein-coupled receptor | 0.101613855 |
| Liver glycogen phosphorylase | Enzyme | 0.101613855 |
| Phenylethanolamine N-methyltransferase | Enzyme | 0.101613855 |
| Neurokinin 2 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Melanocortin receptor 4 | Family A G protein-coupled receptor | 0.101613855 |
| Tyrosine-protein kinase JAK1 | Kinase | 0.101613855 |
| p53-binding protein Mdm-2 | Other nuclear protein | 0.101613855 |
| Protein arginine N-methyltransferase 6 | Writer | 0.101613855 |
| Carbonic anhydrase II | Lyase | 0.101613855 |
| Carbonic anhydrase I | Lyase | 0.101613855 |
| Protein arginine N-methyltransferase 8 | Writer | 0.101613855 |
| Carbonic anhydrase IX | Lyase | 0.101613855 |
| C-C chemokine receptor type 3 | Family A G protein-coupled receptor | 0.101613855 |
| Phospholipase A2 group IIC | Enzyme | 0.101613855 |
| Group X secretory phospholipase A2 | Enzyme | 0.101613855 |
| Cathepsin D | Protease | 0.101613855 |
| Beta-secretase 1 | Protease | 0.101613855 |
| Mitogen-activated protein kinase kinase kinase 12 | Enzyme | 0.101613855 |
| Rho-associated protein kinase 2 | Kinase | 0.101613855 |
| Phosphodiesterase 9A | Phosphodiesterase | 0.101613855 |
| Phosphodiesterase 1C | Phosphodiesterase | 0.101613855 |
| Voltage-gated potassium channel subunit Kv1.3 | Voltage-gated ion channel | 0.101613855 |
| Glucocorticoid receptor | Nuclear receptor | 0.101613855 |
 |
Table 6.
Sitagliptin.
| Target | Target Class | Probability* |
| Dipeptidyl peptidase IV | Protease | 1 |
| Dipeptidyl peptidase VIII | Protease | 1 |
| Fibroblast activation protein alpha | Protease | 1 |
| Dipeptidyl peptidase IX | Protease | 1 |
| Dipeptidyl peptidase II | Protease | 0.115736675 |
| Glycine transporter 1 | Electrochemical transporter | 0.115736675 |
| Chymase | Protease | 0.115736675 |
| C-C chemokine receptor type 2 | Family A G protein-coupled receptor | 0.115736675 |
| Serotonin transporter | Electrochemical transporter | 0.115736675 |
| Histone-arginine methyltransferase CARM1 (by homology) | Writer | 0.115736675 |
| Leukocyte elastase | Protease | 0.115736675 |
| CaM kinase II | Kinase | 0.115736675 |
| Glycine transporter 2 | Electrochemical transporter | 0.115736675 |
| 5-lipoxygenase activating protein | Other cytosolic protein | 0.115736675 |
| Cyclooxygenase-2 | Oxidoreductase | 0.115736675 |
| Gonadotropin-releasing hormone receptor | Family A G protein-coupled receptor | 0.115736675 |
| G-protein coupled bile acid receptor 1 | Family A G protein-coupled receptor | 0.115736675 |
| Beta amyloid A4 protein | Membrane receptor | 0.115736675 |
| Cyclin-dependent kinase 2/cyclin A | Other cytosolic protein | 0.115736675 |
| Histone deacetylase 4 | Eraser | 0.115736675 |
| Interleukin-1 receptor-associated kinase 4 | Kinase | 0.115736675 |
| Metabotropic glutamate receptor 1 | Family C G protein-coupled receptor | 0.115736675 |
| Histone-lysine N-methyltransferase SETD7 | Writer | 0.115736675 |
| C-C chemokine receptor type 1 | Family A G protein-coupled receptor | 0.115736675 |
Group 3. Meglitinides and Target Predictions with Artificial Intelligence. These substances work to reduce blood glucose levels by stimulating endogenous insulin production. The dosing strategy depends on the level of hemoglobin A1c. The recommended starting dose for A1c level below 8% (64 mmol/mol) is 0.5mg pre-prandial and for A1c level above 8% is 1 to 2mg. Two meglitinides are currently available with 73.3% to 86.6% main target prediction.
 |
Table 7.
Nateglinide.
| Target | Target Class | Probability* |
| Solute carrier family 22 member 6 (by homology) | Electrochemical transporter | 0.921392246 |
| Epoxide hydratase | Protease | 0.251528881 |
| Ephrin type-A receptor 2 | Kinase | 0.22658196 |
| Neprilysin | Protease | 0.218248072 |
| Angiotensin-converting enzyme | Protease | 0.151564691 |
| Carboxypeptidase A1 | Protease | 0.134939009 |
| Angiotensin-converting enzyme 2 | Protease | 0.134939009 |
| 11-beta-hydroxysteroid dehydrogenase 1 | Enzyme | 0.126610169 |
| Protein-tyrosine phosphatase 1B | Phosphatase | 0.118277085 |
| T-cell protein-tyrosine phosphatase | Phosphatase | 0.118277085 |
| Calpain 1 | Protease | 0.118277085 |
| 11-beta-hydroxysteroid dehydrogenase 2 | Enzyme | 0.10994577 |
| Protein-tyrosine phosphatase 1C | Phosphatase | 0.10994577 |
| Endothelin-converting enzyme 1 | Protease | 0.101613855 |
| Matrix metalloproteinase 2 | Protease | 0.101613855 |
| Alkaline ceramidase 2 | Enzyme | 0.101613855 |
| Gamma-secretase | Protease | 0.101613855 |
| MAP kinase ERK2 | Kinase | 0.101613855 |
| Integrin alpha-4/beta-1 | Membrane receptor | 0.101613855 |
| Matrix metalloproteinase 3 | Protease | 0.101613855 |
| Matrix metalloproteinase 1 | Protease | 0.101613855 |
| Chymase | Protease | 0.101613855 |
| Estradiol 17-beta-dehydrogenase 2 | Enzyme | 0.101613855 |
| Cyclooxygenase-2 | Oxidoreductase | 0.101613855 |
| Neurotensin receptor 1 | Family A G protein-coupled receptor | 0.101613855 |
| Histone deacetylase 6 | Eraser | 0.101613855 |
| Histone deacetylase 1 | Eraser | 0.101613855 |
| Inhibitor of apoptosis protein 3 | Other cytosolic protein | 0.101613855 |
| Beta secretase 2 | Protease | 0.101613855 |
| Beta-secretase 1 | Protease | 0.101613855 |
| Chromobox protein homolog 7 | Reader | 0.101613855 |
| Protein farnesyltransferase | Enzyme | 0.101613855 |
| Baculoviral IAP repeat-containing protein 2 | Enzyme | 0.101613855 |
| Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 | Enzyme | 0.101613855 |
| HLA class I histocompatibility antigen A-3 | Surface antigen | 0.101613855 |
| Cathepsin D | Protease | 0.101613855 |
| Oxytocin receptor | Family A G protein-coupled receptor | 0.101613855 |
| E3 SUMO-protein ligase CBX4 | Enzyme | 0.101613855 |
| Retinoic acid receptor beta | Nuclear receptor | 0.101613855 |
| Retinoic acid receptor alpha | Nuclear receptor | 0.101613855 |
| G protein-coupled receptor 44 | Family A G protein-coupled receptor | 0.101613855 |
| Cathepsin (B and K) | Protease | 0.101613855 |
| Cannabinoid receptor 1 | Family A G protein-coupled receptor | 0.101613855 |
| Cathepsin G | Protease | 0.101613855 |
| Neurokinin 2 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Aminopeptidase N | Protease | 0.101613855 |
| Aminopeptidase B (by homology) | Protease | 0.101613855 |
| Leucine aminopeptidase | Protease | 0.101613855 |
| Group X secretory phospholipase A2 | Enzyme | 0.101613855 |
| Matrix metalloproteinase 9 | Protease | 0.101613855 |
| Integrin alpha-4/beta-7 | Membrane receptor | 0.101613855 |
| Oxoeicosanoid receptor 1 | Family A G protein-coupled receptor | 0.101613855 |
| Tyrosyl-tRNA synthetase | Enzyme | 0.101613855 |
| Lysine-specific demethylase 5A | Eraser | 0.101613855 |
| Lysine-specific demethylase 5B | Eraser | 0.101613855 |
| Lysine-specific demethylase 2B | Eraser | 0.101613855 |
| Acyl-CoA:dihydroxyacetonephosphateacyltransferase | Enzyme | 0.101613855 |
| Prostanoid EP4 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Serotonin transporter | Electrochemical transporter | 0.101613855 |
| Mu opioid receptor | Family A G protein-coupled receptor | 0.101613855 |
| Delta opioid receptor | Family A G protein-coupled receptor | 0.101613855 |
| Prostanoid EP1 receptor | Family A G protein-coupled receptor | 0.101613855 |
| Aldose reductase (by homology) | Enzyme | 0.101613855 |
| MAP kinase p38 alpha | Kinase | 0.101613855 |
| Solute carrier family 22 member 12 | Electrochemical transporter | 0.101613855 |
| Atrial natriuretic factor | Unclassified protein | 0.101613855 |
| N-acylsphingosine-amidohydrolase | Enzyme | 0.101613855 |
| Leukotriene A4 hydrolase | Protease | 0.101613855 |
| Kappa Opioid receptor | Family A G protein-coupled receptor | 0.101613855 |
| Matrix metalloproteinase 8 | Protease | 0.101613855 |
| Integrin alpha-4 | Membrane receptor | 0.101613855 |
| Transient receptor potential cation channel subfamily M member 8 | Voltage-gated ion channel | 0.101613855 |
| Progesterone receptor | Nuclear receptor | 0.101613855 |
| Lysosomal protective protein | Protease | 0.101613855 |
| Aldo-keto-reductase family 1 member C3 | Enzyme | 0.101613855 |
| Aldo-keto reductase family 1 member C2 | Enzyme | 0.101613855 |
| C-C chemokine receptor type 5 | Family A G protein-coupled receptor | 0.101613855 |
| Dihydroorotate dehydrogenase | Oxidoreductase | 0.101613855 |
| Retinoid X receptor alpha | Nuclear receptor | 0.101613855 |
| Cytochrome P450 26A1 | Cytochrome P450 | 0.101613855 |
| Endothelin receptor ET-A | Family A G protein-coupled receptor | 0.101613855 |
| Cathepsin L | Protease | 0.101613855 |
| Oligopeptide transporter small intestine isoform | Electrochemical transporter | 0.101613855 |
| Cathepsin E | Protease | 0.101613855 |
| Cholecystokinin B receptor | Family A G protein-coupled receptor | 0.101613855 |
| Cyclooxygenase-1 | Oxidoreductase | 0.101613855 |
| Group IIE secretory phospholipase A2 | Enzyme | 0.101613855 |
| Group IIF secretory phospholipase A2 | Enzyme | 0.101613855 |
| Group IID secretory phospholipase A2 | Enzyme | 0.101613855 |
| Phospholipase A2 group 1B (by homology) | Enzyme | 0.101613855 |
| c-Jun N-terminal kinase 1 | Kinase | 0.101613855 |
| Formyl peptide receptor 1 | Family A G protein-coupled receptor | 0.101613855 |
| Dual specificity protein phosphatase 3 | Phosphatase | 0.101613855 |
| Gamma-amino-N-butyrate transaminase (by homology) | Transferase | 0.101613855 |
| Insulin-like growth factor I receptor | Kinase | 0.101613855 |
| Histone deacetylase 8 | Eraser | 0.101613855 |
| Cathepsin (V and K) | Protease | 0.101613855 |
| Phospholipase A2 group IIA | Enzyme | 0.101613855 |
| Transitional endoplasmic reticulum ATPase | Primary active transporter | 0.101613855 |
| Phosphodiesterase 3 | Phosphodiesterase | 0.101613855 |
 |
Table 8.
Rapaglinide.
| Target | Target Class | Probability* |
| Sulfonylurea receptor 1 | Primary active transporter | 0.989973857 |
| Solute carrier family 22 member 1 | Electrochemical transporter | 0.989973857 |
| Hematopoietic prostaglandin D synthase | Transferase | 0.100634432 |
| Vasopressin V2 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Cytosolic phospholipase A2 | Enzyme | 0.100634432 |
| Retinoid X receptor alpha | Nuclear receptor | 0.100634432 |
| ADAMTS5 | Protease | 0.100634432 |
| Matrix metalloproteinase 14 | Protease | 0.100634432 |
| Peroxisome proliferator-activated receptor delta | Nuclear receptor | 0.100634432 |
| Sphingosine 1-phosphate receptor Edg-1 | Family A G protein-coupled receptor | 0.100634432 |
| Neurotensin receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Epoxide hydrolase 1 | Protease | 0.100634432 |
| Phosphodiesterase 4D | Phosphodiesterase | 0.100634432 |
| Phosphodiesterase 4C | Phosphodiesterase | 0.100634432 |
| 11-beta-hydroxysteroid dehydrogenase 1 | Enzyme | 0.100634432 |
| Thromboxane-A synthase | Cytochrome P450 | 0.100634432 |
| Arachidonate 5-lipoxygenase | Oxidoreductase | 0.100634432 |
| Prostaglandin E synthase | Enzyme | 0.100634432 |
| Retinoid X receptor gamma (by homology) | Nuclear receptor | 0.100634432 |
| Heat shock protein HSP 90-alpha | Other cytosolic protein | 0.100634432 |
| Cathepsin (B and K) | Protease | 0.100634432 |
| Plasma kallikrein | Protease | 0.100634432 |
| Complement factor D | Protease | 0.100634432 |
| Sphingosine 1-phosphate receptor Edg-6 | Family A G protein-coupled receptor | 0.100634432 |
| Matrix metalloproteinase 8 | Protease | 0.100634432 |
| Kelch-like ECH-associated protein 1 | Unclassified protein | 0.100634432 |
| Dual specificity phosphatase Cdc25A | Phosphatase | 0.100634432 |
| Retinoid X receptor beta | Nuclear receptor | 0.100634432 |
| Macrophage migration inhibitory factor | Enzyme | 0.100634432 |
| Cysteinyl leukotriene receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Alpha-2b adrenergic receptor | Family A G protein-coupled receptor | 0.100634432 |
| Adenosine A1 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Nitric oxide synthase, inducible | Enzyme | 0.100634432 |
| Purinergic receptor P2Y12 | Family A G protein-coupled receptor | 0.100634432 |
| Ubiquitin-like domain-containing CTD phosphatase 1 | Enzyme | 0.100634432 |
| Retinoic acid receptor alpha | Nuclear receptor | 0.100634432 |
| Monoacylglycerol lipase ABHD6 (by homology) | Enzyme | 0.100634432 |
| Low molecular weight phosphotyrosine protein phosphatase | Phosphatase | 0.100634432 |
| Peptidyl-glycine alpha-amidating monooxygenase | Enzyme | 0.100634432 |
| Vasopressin V1a receptor | Family A G protein-coupled receptor | 0.100634432 |
| Ileal bile acid transporter | Electrochemical transporter | 0.100634432 |
| Translocator protein (by homology) | Membrane receptor | 0.100634432 |
| Serine/threonine-protein phosphatase | Phosphatase | 0.100634432 |
| Endothelin-converting enzyme 1 | Protease | 0.100634432 |
| Leukotriene B4 receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Cytochrome P450 26A1 | Cytochrome P450 | 0.100634432 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.100634432 |
| Phospholipase A2 group IIA | Enzyme | 0.100634432 |
| Gamma-secretase | Protease | 0.100634432 |
| Carboxypeptidase B | Protease | 0.100634432 |
| Cytochrome P450 26B1 | Cytochrome P450 | 0.100634432 |
| Cathepsin G | Protease | 0.100634432 |
| Tumour suppressor p53/oncoprotein Mdm2 | Transcription factor | 0.100634432 |
| Thrombopoietin receptor | Membrane receptor | 0.100634432 |
| Inhibitor of nuclear factor kappa B kinase beta subunit | Kinase | 0.100634432 |
| SUMO-activating enzyme | Enzyme | 0.100634432 |
| Hexokinase type IV | Enzyme | 0.100634432 |
| Anandamide amidohydrolase | Enzyme | 0.100634432 |
| Fatty acid binding protein epidermal | Fatty acid binding protein family | 0.100634432 |
| Prostanoid EP3 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Prostaglandin E synthase 2 | Enzyme | 0.100634432 |
| c-Jun N-terminal kinase 1 | Kinase | 0.100634432 |
| Phosphodiesterase 2A | Phosphodiesterase | 0.100634432 |
| Transitional endoplasmic reticulum ATPase | Primary active transporter | 0.100634432 |
| Sn1-specific diacylglycerol lipase alpha | Enzyme | 0.100634432 |
| Prostanoid EP4 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Lysine-specific demethylase 5C | Eraser | 0.100634432 |
| Casein kinase II alpha | Kinase | 0.100634432 |
| Presenilin 1 | Other ion channel | 0.100634432 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.100634432 |
| Urokinase plasminogen activator surface receptor | Membrane receptor | 0.100634432 |
| Lysosomal protective protein | Protease | 0.100634432 |
| Somatostatin receptor 3 | Family A G protein-coupled receptor | 0.100634432 |
| Toll-like receptor 4 | Toll-like and Il-1 receptors | 0.100634432 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.100634432 |
| Free fatty acid receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 | Enzyme | 0.100634432 |
| Apelin receptor | Family A G protein-coupled receptor | 0.100634432 |
| Glycogen synthase kinase-3 alpha | Kinase | 0.100634432 |
| L-lactate dehydrogenase A chain | Enzyme | 0.100634432 |
| LIM domain kinase 2 | Kinase | 0.100634432 |
| Cyclooxygenase-1 | Oxidoreductase | 0.100634432 |
| Cyclooxygenase-2 (by homology) | Oxidoreductase | 0.100634432 |
| 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 | Enzyme | 0.100634432 |
| Dual specificity phosphatase Cdc25C | Phosphatase | 0.100634432 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.100634432 |
| Aldo-keto-reductase family 1 member C3 | Enzyme | 0.100634432 |
| Dual specificity phosphatase Cdc25B | Phosphatase | 0.100634432 |
| G protein-coupled receptor 44 | Family A G protein-coupled receptor | 0.100634432 |
| Oxoeicosanoid receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.100634432 |
| Plasminogen activator inhibitor-1 | Secreted protein | 0.100634432 |
| HMG-CoA reductase (by homology) | Oxidoreductase | 0.100634432 |
| Taste receptor type 2 member 31 | Taste family G protein-coupled receptor | 0.100634432 |
| DNA polymerase beta (by homology) | Enzyme | 0.100634432 |
| PI3-kinase p110-beta subunit | Enzyme | 0.100634432 |
| Prolyl endopeptidase | Protease | 0.100634432 |
| Cathepsin (V and K) | Protease | 0.100634432 |
| Gonadotropin-releasing hormone receptor | Family A G protein-coupled receptor | 0.100634432 |
GROUP 4. Non-sulfonylureas and Target Predictions with Artificial Intelligence. It inhibits the amount of glucose produced by the liver, increases the insulin-receptor binding and stimulates tissue uptake of glucose. One antidiabetic agent of this class is currently available (86.6% main target prediction).
 |
Table 9.
Metformin.
| Target | Target Class | Probability* |
| Thrombin | Protease | 0.02383274 |
| Urokinase-type plasminogen activator | Protease | 0 |
| Histamine H4 receptor | Family A G protein-coupled receptor | 0 |
| D-amino-acid oxidase | Enzyme | 0 |
| Histamine H3 receptor | Family A G protein-coupled receptor | 0 |
| Xanthine dehydrogenase | Oxidoreductase | 0 |
| Dihydrofolate reductase (by homology) | Oxidoreductase | 0 |
| Integrin alpha-V/beta-3 | Membrane receptor | 0 |
| Coagulation factor IX | Protease | 0 |
| Neuronal acetylcholine receptor; alpha4/beta2 | Ligand-gated ion channel | 0 |
| S-100 protein beta chain | Other cytosolic protein | 0 |
| Beta-hexosaminidase subunit alpha | Enzyme | 0 |
| Beta-N-acetyl-D-hexosaminidase-A/B | Enzyme | 0 |
| Solute carrier family 22 member 1 (by homology) | Electrochemical transporter | 0 |
| Multidrug and toxin extrusion protein 1 (by homology) | Electrochemical transporter | 0 |
| Trypsin I | Protease | 0 |
| Indolethylamine N-methyltransferase | Enzyme | 0 |
| 7,8-dihydro-8-oxoguanine triphosphatase | Enzyme | 0 |
| Thymidine phosphorylase | Enzyme | 0 |
| Dihydropyrimidine dehydrogenase | Enzyme | 0 |
| Adenosine A1 receptor (by homology) | Family A G protein-coupled receptor | 0 |
| Serotonin 5a (5-HT5a) receptor | Family A G protein-coupled receptor | 0 |
| CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) | Kinase | 0 |
| Nitric oxide synthase, inducible | Enzyme | 0 |
| Nitric-oxide synthase, endothelial | Enzyme | 0 |
| Indoleamine 2,3-dioxygenase | Enzyme | 0 |
| Neuronal acetylcholine receptor protein alpha-4 subunit (by homology) | Ligand-gated ion channel | 0 |
| Estrogen receptor beta | Nuclear receptor | 0 |
| Histamine H2 receptor | Family A G protein-coupled receptor | 0 |
| Uridine phosphorylase 1 (by homology) | Enzyme | 0 |
| Carbonic anhydrase II | Lyase | 0 |
| Carbonic anhydrase I | Lyase | 0 |
| Carbonic anhydrase XII | Lyase | 0 |
| Carbonic anhydrase IX | Lyase | 0 |
| G-protein coupled receptor 84 | Family A G protein-coupled receptor | 0 |
| Purine nucleoside phosphorylase | Enzyme | 0 |
| Trace amine-associated receptor 1 (by homology) | Family A G protein-coupled receptor | 0 |
| Nitric-oxide synthase, brain | Enzyme | 0 |
| Nischarin | Other cytosolic protein | 0 |
| Plasminogen | Protease | 0 |
| Thymidylate synthase | Transferase | 0 |
| Kallikrein 1 | Protease | 0 |
| Methionine aminopeptidase 2 | Protease | 0 |
| Phosphodiesterase 5A | Phosphodiesterase | 0 |
| Epidermal growth factor receptor erbB1 | Kinase | 0 |
| Guanine deaminase | Hydrolase | 0 |
| Urokinase plasminogen activator surface receptor | Membrane receptor | 0 |
| Acetylcholinesterase | Hydrolase | 0 |
Group 5. Sodium-Glucose-co Transporter 2 (SGLT-2) inhibitors and Target Predictions with Artificial Intelligence. SGLT2 inhibitors are the latest class of anti-hyperglycemic agents approved by Food and Drug Administration (FDA). SGLT2 inhibitors function through a novel mechanism consisting of reducing renal tubular glucose reabsorption. Hence, they help to reduce blood glucose without stimulating insulin release. Currently, there are four antidiabetic agents of this class with 73.3% to 86.6% main target prediction.
 |
Table 10.
Canagliflozin.
| Target | Target Class | Probability* |
| Sodium/glucose cotransporter 2 | Electrochemical transporter | 0.830720846 |
| Sodium/glucose cotransporter 1 | Electrochemical transporter | 0.778528112 |
| Glucose transporter (by homology) | Electrochemical transporter | 0.118883307 |
| Equilibrative nucleoside transporter 1 | Electrochemical transporter | 0.118883307 |
| Coagulation factor VII/tissue factor | Surface antigen | 0.118883307 |
| Adenosine A1 receptor (by homology) | Family A G protein-coupled receptor | 0.118883307 |
| Adenosine kinase | Enzyme | 0.118883307 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.118883307 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.118883307 |
| Sodium/nucleoside cotransporter 2 | Electrochemical transporter | 0.118883307 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.118883307 |
| Purinergic receptor P2Y12 (by homology) | Family A G protein-coupled receptor | 0.118883307 |
| MAP kinase p38 alpha | Kinase | 0.118883307 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.118883307 |
| Glyceraldehyde-3-phosphate dehydrogenase liver | Oxidoreductase | 0.118883307 |
| Carbonic anhydrase II | Lyase | 0.118883307 |
| Carbonic anhydrase I | Lyase | 0.118883307 |
| Carbonic anhydrase IX | Lyase | 0.118883307 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.118883307 |
| Liver glycogen phosphorylase | Enzyme | 0.118883307 |
| Interleukin-1 receptor-associated kinase 4 | Kinase | 0.118883307 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.118883307 |
| Bifunctional protein NCOAT | Enzyme | 0.118883307 |
| Uridine phosphorylase 1 (by homology) | Enzyme | 0.118883307 |
| DNA (cytosine-5)-methyltransferase 1 | Writer | 0.118883307 |
| Beta-glucocerebrosidase | Enzyme | 0.118883307 |
| Carbonic anhydrase XII | Lyase | 0.118883307 |
| Carbonic anhydrase XIV | Lyase | 0.118883307 |
| Heat shock cognate 71 kDa protein | Other cytosolic protein | 0.118883307 |
| 78 kDa glucose-regulated protein | Unclassified protein | 0.118883307 |
| Hepatocyte growth factor receptor | Kinase | 0.118883307 |
| Galectin-3 | Other cytosolic protein | 0.118883307 |
| Galectin-1 | Other cytosolic protein | 0.118883307 |
| Muscle glycogen phosphorylase | Enzyme | 0.118883307 |
| Beta-glucosidase | Enzyme | 0.118883307 |
| Protein arginine N-methyltransferase 7 | Writer | 0.118883307 |
| Serine/threonine-protein kinase Chk1 | Kinase | 0.118883307 |
| c-Jun N-terminal kinase 1 | Kinase | 0.118883307 |
| Leucyl-tRNA synthetase | Enzyme | 0.118883307 |
| MAP kinase ERK2 | Kinase | 0.118883307 |
| Serine/threonine-protein kinase B-raf | Kinase | 0.118883307 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.118883307 |
| Dipeptidyl peptidase IV | Protease | 0.118883307 |
| Sodium channel protein type IX alpha subunit | Voltage-gated ion channel | 0.118883307 |
| NAD-dependent deacetylase sirtuin 2 | Eraser | 0.118883307 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Enzyme | 0.118883307 |
| Cathepsin L | Protease | 0.118883307 |
| Glutamate [NMDA] receptor PROTEIN | Ligand-gated ion channel | 0.118883307 |
| Matrix metalloproteinase 13 | Protease | 0.118883307 |
| Matrix metalloproteinase 9 | Protease | 0.118883307 |
| Matrix metalloproteinase 2 | Protease | 0.118883307 |
| Matrix metalloproteinase 8 | Protease | 0.118883307 |
| Tyrosine-protein kinase SYK | Kinase | 0.118883307 |
 |
Table 11.
Dapaglifozin.
| Target | Target Class | Probability* |
| Sodium/myo-inositol cotransporter 2 | Electrochemical transporter | 1 |
| Low affinity sodium-glucose cotransporter | Electrochemical transporter | 1 |
| Sodium/glucose cotransporter 2 | Electrochemical transporter | 1 |
| Sodium/glucose cotransporter 1 | Electrochemical transporter | 1 |
| Adenosine kinase | Enzyme | 0.115736675 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.115736675 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.115736675 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.115736675 |
| Platelet-derived growth factor receptor beta | Kinase | 0.115736675 |
| Tyrosine-protein kinase LCK | Kinase | 0.115736675 |
| MAP kinase p38 alpha | Kinase | 0.115736675 |
| c-Jun N-terminal kinase 3 | Kinase | 0.115736675 |
| MAP kinase p38 beta | Kinase | 0.115736675 |
| Ephrin type-A receptor 5 | Kinase | 0.115736675 |
| Serine/threonine-protein kinase GAK | Kinase | 0.115736675 |
| Equilibrative nucleoside transporter 1 | Electrochemical transporter | 0.115736675 |
| Beta-glucosidase | Enzyme | 0.115736675 |
| Hexokinase type II | Enzyme | 0.115736675 |
| Hexokinase type I | Enzyme | 0.115736675 |
| Sodium/nucleoside cotransporter 2 | Electrochemical transporter | 0.115736675 |
| 78 kDa glucose-regulated protein | Unclassified protein | 0.115736675 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.115736675 |
| Heat shock cognate 71 kDa protein | Other cytosolic protein | 0.115736675 |
| Coagulation factor VII/tissue factor | Surface antigen | 0.115736675 |
| Beta-glucocerebrosidase | Enzyme | 0.115736675 |
| Glucose transporter (by homology) | Electrochemical transporter | 0.115736675 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.115736675 |
| Uridine phosphorylase 1 (by homology) | Enzyme | 0.115736675 |
| Alkaline phosphatase, tissue-nonspecific isozyme | Enzyme | 0.115736675 |
| Muscle glycogen phosphorylase | Enzyme | 0.115736675 |
| Glyceraldehyde-3-phosphate dehydrogenase liver | Oxidoreductase | 0.115736675 |
| Glutathione S-transferase Pi | Enzyme | 0.115736675 |
| Glutathione S-transferase Mu 2 | Enzyme | 0.115736675 |
| Matrix metalloproteinase 3 | Protease | 0.115736675 |
| Matrix metalloproteinase 1 | Protease | 0.115736675 |
| Serine/threonine-protein kinase Chk1 | Kinase | 0.115736675 |
| Bifunctional protein NCOAT | Enzyme | 0.115736675 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.115736675 |
| Cathepsin L | Protease | 0.115736675 |
| Purinergic receptor P2Y12 (by homology) | Family A G protein-coupled receptor | 0.115736675 |
| Intercellular adhesion molecule-1 | Adhesion | 0.115736675 |
| Vascular cell adhesion protein 1 | Adhesion | 0.115736675 |
| Selectin E | Adhesion | 0.115736675 |
| MAP kinase ERK2 | Kinase | 0.115736675 |
| Liver glycogen phosphorylase | Enzyme | 0.115736675 |
| Interleukin-1 receptor-associated kinase 4 | Kinase | 0.115736675 |
| Glutamate [NMDA] receptor PROTEIN | Ligand-gated ion channel | 0.115736675 |
| Carbonic anhydrase XIV | Lyase | 0.115736675 |
| Neprilysin | Protease | 0.115736675 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.115736675 |
| Mitogen-activated protein kinase kinase kinase 14 | Kinase | 0.115736675 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.115736675 |
| Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase | Enzyme | 0.115736675 |
| Alpha-mannosidase 2A1 | Enzyme | 0.115736675 |
| Alpha-L-fucosidase I | Enzyme | 0.115736675 |
| Endothelin-converting enzyme 1 | Protease | 0.115736675 |
| Glutamate receptor ionotropic kainate 1 | Ligand-gated ion channel | 0.115736675 |
| Beta-galactosidase | Hydrolase | 0.115736675 |
| Cyclin-dependent kinase 1 | Kinase | 0.115736675 |
| Squalene synthetase | Enzyme | 0.115736675 |
 |
Table 12.
Empagliflozin.
| Target | Target Class | Probability* |
| Sodium/glucose cotransporter 2 | Electrochemical transporter | 0.995022825 |
| Sodium/glucose cotransporter 1 | Electrochemical transporter | 0.995022825 |
| Sodium/myo-inositol cotransporter 2 | Electrochemical transporter | 0.424564571 |
| Low affinity sodium-glucose cotransporter | Electrochemical transporter | 0.424564571 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.118883307 |
| Adenosine kinase | Enzyme | 0.118883307 |
| Equilibrative nucleoside transporter 1 | Electrochemical transporter | 0.118883307 |
| Neprilysin (by homology) | Protease | 0.118883307 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.118883307 |
| Glucose transporter (by homology) | Electrochemical transporter | 0.118883307 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.118883307 |
| Coagulation factor VII/tissue factor | Surface antigen | 0.118883307 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.118883307 |
| Purinergic receptor P2Y12 | Family A G protein-coupled receptor | 0.118883307 |
| Ceramide glucosyltransferase | Transferase | 0.118883307 |
| Beta-glucocerebrosidase | Enzyme | 0.118883307 |
| Beta-glucosidase | Enzyme | 0.118883307 |
 |
Table 13.
Ertugliflozin.
| Target | Target Class | Probability* |
| Low affinity sodium-glucose cotransporter | Electrochemical transporter | 1 |
| Sodium/glucose cotransporter 1 | Electrochemical transporter | 1 |
| Sodium/glucose cotransporter 2 (by homology) | Electrochemical transporter | 0.930927137 |
| Sodium/myo-inositol cotransporter 2 | Electrochemical transporter | 0.214435241 |
| Glucose transporter (by homology) | Electrochemical transporter | 0.106165761 |
| Adenosine kinase | Enzyme | 0.106165761 |
| Equilibrative nucleoside transporter 1 | Electrochemical transporter | 0.106165761 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.106165761 |
| Carbonic anhydrase II | Lyase | 0.106165761 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.106165761 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.106165761 |
| Carbonic anhydrase I | Lyase | 0.106165761 |
| Carbonic anhydrase XII | Lyase | 0.106165761 |
| Carbonic anhydrase IX | Lyase | 0.106165761 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.106165761 |
| Heat shock cognate 71 kDa protein | Other cytosolic protein | 0.106165761 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.106165761 |
| Muscle glycogen phosphorylase | Enzyme | 0.106165761 |
| 78 kDa glucose-regulated protein | Unclassified protein | 0.106165761 |
| Beta-glucocerebrosidase | Enzyme | 0.106165761 |
| Matrix metalloproteinase 3 | Protease | 0.106165761 |
| Matrix metalloproteinase 9 | Protease | 0.106165761 |
| Matrix metalloproteinase 1 | Protease | 0.106165761 |
| ADAM17 | Protease | 0.106165761 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.106165761 |
| Hexokinase type II | Enzyme | 0.106165761 |
| Hexokinase type I | Enzyme | 0.106165761 |
| Uridine phosphorylase 1 (by homology) | Enzyme | 0.106165761 |
| Purinergic receptor P2Y12 (by homology) | Family A G protein-coupled receptor | 0.106165761 |
| Sodium/nucleoside cotransporter 2 | Electrochemical transporter | 0.106165761 |
| MAP kinase p38 alpha | Kinase | 0.106165761 |
| Coagulation factor VII/tissue factor | Surface antigen | 0.106165761 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.106165761 |
| Carbonic anhydrase XIV | Lyase | 0.106165761 |
| Glyceraldehyde-3-phosphate dehydrogenase liver | Oxidoreductase | 0.106165761 |
| Adenosine A1 receptor | Family A G protein-coupled receptor | 0.106165761 |
| Bifunctional protein NCOAT | Enzyme | 0.106165761 |
| 6-O-methylguanine-DNA methyltransferase | Enzyme | 0.106165761 |
| Beta-mannosidase | Enzyme | 0.106165761 |
| Matrix metalloproteinase 13 | Protease | 0.106165761 |
| Cyclin-dependent kinase 2 | Kinase | 0.106165761 |
| Cyclin-dependent kinase 1 | Kinase | 0.106165761 |
| Matrix metalloproteinase 7 | Protease | 0.106165761 |
| Matrix metalloproteinase 12 | Protease | 0.106165761 |
| Matrix metalloproteinase 8 | Protease | 0.106165761 |
| Neprilysin | Protease | 0.106165761 |
| GTPase NRas | Unclassified protein | 0.106165761 |
| Tyrosine-protein kinase SRC | Kinase | 0.106165761 |
| Endothelin-converting enzyme 1 | Protease | 0.106165761 |
| Platelet-derived growth factor receptor beta | Kinase | 0.106165761 |
| Tyrosine-protein kinase LCK | Kinase | 0.106165761 |
| c-Jun N-terminal kinase 3 | Kinase | 0.106165761 |
| MAP kinase p38 beta | Kinase | 0.106165761 |
| Ephrin type-A receptor 5 | Kinase | 0.106165761 |
| Serine/threonine-protein kinase GAK | Kinase | 0.106165761 |
| Type-1 angiotensin II receptor (by homology) | Family A G protein-coupled receptor | 0.106165761 |
| Alpha-L-fucosidase I | Enzyme | 0.106165761 |
| Fibroblast growth factor receptor 1 | Kinase | 0.106165761 |
| DNA (cytosine-5)-methyltransferase 1 | Writer | 0.106165761 |
| Glutamate [NMDA] receptor PROTEIN | Ligand-gated ion channel | 0.106165761 |
| Serine/threonine-protein kinase Chk1 | Kinase | 0.106165761 |
| Interleukin-1 receptor-associated kinase 4 | Kinase | 0.106165761 |
| MAP kinase ERK2 | Kinase | 0.106165761 |
Group 6. Sulfonylureas and meglitinides and Target Predictions with Artificial Intelligence. This group of diabetic agents directly stimulate insulin release from pancreatic beta cells; thus, lower blood glucose concentration. Because they work by stimulating insulin secretion, they are useful only in patients with some beta cell function. Adverse effects may include weight gain and hypoglycemia. Six antidiabetic agents of this class are currently available (53.3% to 86.6% main target prediction).
 |
Table 14.
Glimepiride.
| Target | Target Class | Probability* |
| Prostanoid EP4 receptor | Family A G protein-coupled receptor | 0.120225751 |
| Proteasome subunit beta type-9 | Enzyme | 0.120225751 |
| Tyrosine-protein kinase BRK | Kinase | 0.120225751 |
| Tyrosine-protein kinase ABL | Kinase | 0.120225751 |
| Insulin-like growth factor I receptor | Kinase | 0.120225751 |
| Insulin receptor | Kinase | 0.120225751 |
| Cannabinoid receptor 2 | Family A G protein-coupled receptor | 0.120225751 |
| Tyrosine-protein kinase SRC | Kinase | 0.120225751 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.120225751 |
| PI3-kinase p110-delta subunit | Enzyme | 0.120225751 |
| PI3-kinase p110-beta subunit | Enzyme | 0.120225751 |
| PI3-kinase p110-gamma subunit | Enzyme | 0.120225751 |
| Hepatocyte growth factor receptor | Kinase | 0.120225751 |
| PI3-kinase p110-alpha subunit | Enzyme | 0.120225751 |
| Fibroblast growth factor receptor 2 | Kinase | 0.120225751 |
| ALK tyrosine kinase receptor | Kinase | 0.120225751 |
| Mitogen-activated protein kinase kinase kinase 12 | Enzyme | 0.120225751 |
| Acetyl-CoA carboxylase 2 | Ligase | 0.120225751 |
| Cathepsin S | Protease | 0.120225751 |
| Acetyl-coenzyme A transporter 1 | Electrochemical transporter | 0.120225751 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.120225751 |
| c-Jun N-terminal kinase 1 | Kinase | 0.120225751 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.120225751 |
| c-Jun N-terminal kinase 2 | Kinase | 0.120225751 |
| MAP kinase p38 alpha | Kinase | 0.120225751 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.120225751 |
| Tyrosine kinase non-receptor protein 2 | Kinase | 0.120225751 |
| Fatty acid synthase | Transferase | 0.120225751 |
| Receptor protein-tyrosine kinase erbB-2 | Kinase | 0.120225751 |
| Macrophage colony stimulating factor receptor | Kinase | 0.120225751 |
| Platelet-derived growth factor receptor beta | Kinase | 0.120225751 |
| Purinergic receptor P2Y12 | Family A G protein-coupled receptor | 0.120225751 |
| Cyclin-dependent kinase 4 | Kinase | 0.120225751 |
| Orexin receptor 2 | Family A G protein-coupled receptor | 0.120225751 |
| Nicotinamide phosphoribosyltransferase | Enzyme | 0.120225751 |
| Calcium sensing receptor | Family C G protein-coupled receptor | 0.120225751 |
| Muscarinic acetylcholine receptor M2 | Family A G protein-coupled receptor | 0.120225751 |
| Muscarinic acetylcholine receptor M3 | Family A G protein-coupled receptor | 0.120225751 |
| Gamma-secretase | Protease | 0.120225751 |
| Endothelin receptor ET-B | Family A G protein-coupled receptor | 0.120225751 |
| Androgen Receptor | Nuclear receptor | 0.120225751 |
| Serine/threonine-protein kinase RAF | Kinase | 0.120225751 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.120225751 |
| Stem cell growth factor receptor | Kinase | 0.120225751 |
| Progesterone receptor | Nuclear receptor | 0.120225751 |
| Endothelin receptor ET-A | Family A G protein-coupled receptor | 0.120225751 |
| Nerve growth factor receptor Trk-A | Kinase | 0.120225751 |
| Phosphoglycerate kinase 1 | Enzyme | 0.120225751 |
| Vanilloid receptor | Voltage-gated ion channel | 0.120225751 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.120225751 |
| EZH2/SUZ12/EED/RBBP7/RBBP4 | Writer | 0.120225751 |
| 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 | Enzyme | 0.120225751 |
| Tyrosine-protein kinase SYK | Kinase | 0.120225751 |
| Orexin receptor 1 | Family A G protein-coupled receptor | 0.120225751 |
| Metabotropic glutamate receptor 5 | Family C G protein-coupled receptor | 0.120225751 |
| Interleukin-1 receptor-associated kinase 4 | Kinase | 0.120225751 |
| N-acylsphingosine-amidohydrolase | Enzyme | 0.120225751 |
| Beta-secretase 1 | Protease | 0.120225751 |
| Dual specificity protein kinase TTK | Kinase | 0.120225751 |
| Muscle glycogen synthase | Enzyme | 0.120225751 |
| Bromodomain-containing protein 4 | Reader | 0.120225751 |
| Tyrosine-protein kinase JAK3 | Kinase | 0.120225751 |
| Focal adhesion kinase 1 | Kinase | 0.120225751 |
| Phosphodiesterase 9A | Phosphodiesterase | 0.120225751 |
| MAP kinase ERK2 | Kinase | 0.120225751 |
| P2X purinoceptor 7 | Ligand-gated ion channel | 0.120225751 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.120225751 |
| Serine/threonine-protein kinase mTOR | Kinase | 0.120225751 |
| Squalene synthetase | Enzyme | 0.120225751 |
| Phosphodiesterase 1C | Phosphodiesterase | 0.120225751 |
| Polyadenylate-binding protein 1 | Unclassified protein | 0.120225751 |
| Vasopressin V2 receptor (by homology) | Family A G protein-coupled receptor | 0.120225751 |
| Gonadotropin-releasing hormone receptor | Family A G protein-coupled receptor | 0.120225751 |
| Oxytocin receptor (by homology) | Family A G protein-coupled receptor | 0.120225751 |
| 3-phosphoinositide dependent protein kinase-1 | Kinase | 0.120225751 |
| Rho-associated protein kinase 2 | Kinase | 0.120225751 |
| Cyclin-dependent kinase 1/cyclin B1 | Other cytosolic protein | 0.120225751 |
| Cyclin-dependent kinase 2/cyclin A | Other cytosolic protein | 0.120225751 |
| Cyclin T1 | Other cytosolic protein | 0.120225751 |
| Cyclin-dependent kinase 7/ cyclin H | Other cytosolic protein | 0.120225751 |
| CDK9/cyclin T1 | Other cytosolic protein | 0.120225751 |
| Glycogen synthase kinase-3 beta | Kinase | 0.120225751 |
| Cyclin-dependent kinase 2 | Kinase | 0.120225751 |
| CDK2/Cyclin A | Kinase | 0.120225751 |
| Protein kinase C beta | Kinase | 0.120225751 |
| Caspase-6 | Protease | 0.120225751 |
| Caspase-7 | Protease | 0.120225751 |
| Hexokinase type IV | Enzyme | 0.120225751 |
| TGF-beta receptor type II | Kinase | 0.120225751 |
| Caspase-1 | Protease | 0.120225751 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.120225751 |
| Smoothened homolog | Frizzled family G protein-coupled receptor | 0.120225751 |
| Glycine transporter 1 | Electrochemical transporter | 0.120225751 |
| Tyrosine-protein kinase ITK/TSK | Kinase | 0.120225751 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.120225751 |
| Protein Wnt-3a | Unclassified protein | 0.120225751 |
| Estrogen receptor alpha | Nuclear receptor | 0.120225751 |
| Estrogen receptor beta | Nuclear receptor | 0.120225751 |
| Tankyrase-2 | Enzyme | 0.120225751 |
| DNA-dependent protein kinase | Kinase | 0.120225751 |
 |
Table 15.
Glipizide.
| Target | Target Class | Probability* |
| Tyrosine-protein kinase JAK3 | Kinase | 0.118883307 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.118883307 |
| Serotonin 7 (5-HT7) receptor | Family A G protein-coupled receptor | 0.118883307 |
| Serine/threonine-protein kinase mTOR | Kinase | 0.118883307 |
| Vascular endothelial growth factor receptor 1 | Kinase | 0.118883307 |
| Platelet-derived growth factor receptor alpha | Kinase | 0.118883307 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.118883307 |
| Fibroblast growth factor receptor 1 | Kinase | 0.118883307 |
| Prostanoid EP3 receptor | Family A G protein-coupled receptor | 0.118883307 |
| Sodium channel protein type IX alpha subunit | Voltage-gated ion channel | 0.118883307 |
| MAP kinase p38 alpha | Kinase | 0.118883307 |
| Bromodomain-containing protein 2 | Reader | 0.118883307 |
| Bromodomain-containing protein 3 | Reader | 0.118883307 |
| Phosphodiesterase 4B | Phosphodiesterase | 0.118883307 |
| CREB-binding protein/p53 | Writer | 0.118883307 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.118883307 |
| Platelet-derived growth factor receptor beta | Kinase | 0.118883307 |
| Inhibitor of nuclear factor kappa B kinase beta subunit | Kinase | 0.118883307 |
| Complement factor D | Protease | 0.118883307 |
| Adenosine A1 receptor (by homology) | Family A G protein-coupled receptor | 0.118883307 |
| Hepatocyte growth factor receptor | Kinase | 0.118883307 |
| Vascular endothelial growth factor receptor 3 | Kinase | 0.118883307 |
| Phosphodiesterase 9A | Phosphodiesterase | 0.118883307 |
| Angiotensin II receptor | Family A G protein-coupled receptor | 0.118883307 |
| Phosphodiesterase 4A | Phosphodiesterase | 0.118883307 |
| Tyrosine-protein kinase SYK | Kinase | 0.118883307 |
| Bradykinin B1 receptor | Family A G protein-coupled receptor | 0.118883307 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.118883307 |
| Insulin-like growth factor I receptor | Kinase | 0.118883307 |
| Oxytocin receptor | Family A G protein-coupled receptor | 0.118883307 |
| c-Jun N-terminal kinase 3 | Kinase | 0.118883307 |
| Cathepsin S | Protease | 0.118883307 |
| MAP kinase ERK2 | Kinase | 0.118883307 |
| Hypoxia-inducible factor 1 alpha | Transcription factor | 0.118883307 |
| Tyrosine kinase non-receptor protein 2 | Kinase | 0.118883307 |
| Purinergic receptor P2Y12 | Family A G protein-coupled receptor | 0.118883307 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.118883307 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.118883307 |
| 11-beta-hydroxysteroid dehydrogenase 1 | Enzyme | 0.118883307 |
| Platelet activating factor receptor | Family A G protein-coupled receptor | 0.118883307 |
| Nerve growth factor receptor Trk-A | Kinase | 0.118883307 |
| Vanilloid receptor | Voltage-gated ion channel | 0.118883307 |
| CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) | Kinase | 0.118883307 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.118883307 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.118883307 |
| DNA-dependent protein kinase | Kinase | 0.118883307 |
| Cathepsin (V and K) (by homology) | Protease | 0.118883307 |
| Ribosomal protein S6 kinase 1 | Kinase | 0.118883307 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.118883307 |
| Phosphatidylinositol 3-kinase catalytic subunit type 3 | Enzyme | 0.118883307 |
| CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) | Kinase | 0.118883307 |
| c-Jun N-terminal kinase 1 | Kinase | 0.118883307 |
| c-Jun N-terminal kinase 2 | Kinase | 0.118883307 |
| Leucine-rich repeat serine/threonine-protein kinase 2 | Kinase | 0.118883307 |
| Calcium sensing receptor | Family C G protein-coupled receptor | 0.118883307 |
| Proteasome subunit beta type-9 | Enzyme | 0.118883307 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.118883307 |
| Intercellular adhesion molecule-1 | Adhesion | 0.118883307 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.118883307 |
| Selectin E | Adhesion | 0.118883307 |
| Rho-associated protein kinase 2 | Kinase | 0.118883307 |
| Cyclin-dependent kinase 2 | Kinase | 0.118883307 |
| Transcription intermediary factor 1-alpha | Reader | 0.118883307 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.118883307 |
| Cytochrome P450 19A1 | Cytochrome P450 | 0.118883307 |
| Protein kinase C theta | Kinase | 0.118883307 |
| TGF-beta receptor type I | Kinase | 0.118883307 |
| Serine/threonine-protein kinase TNNI3K | Kinase | 0.118883307 |
| Cyclin-dependent kinase 2/cyclin E1 | Kinase | 0.118883307 |
| Glycine transporter 1 | Electrochemical transporter | 0.118883307 |
| Glycine transporter 2 | Electrochemical transporter | 0.118883307 |
| N-acylsphingosine-amidohydrolase (by homology) | Enzyme | 0.118883307 |
| Acetyl-CoA carboxylase 2 | Ligase | 0.118883307 |
| Matrix metalloproteinase 1 | Protease | 0.118883307 |
| Probable protein-cysteine N-palmitoyltransferase porcupine (by homology) | Enzyme | 0.118883307 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.118883307 |
| Tyrosine-protein kinase LCK | Kinase | 0.118883307 |
| Cyclin-dependent kinase 1 | Kinase | 0.118883307 |
| Cyclin-dependent kinase 4 | Kinase | 0.118883307 |
| Protein-tyrosine phosphatase 1B | Phosphatase | 0.118883307 |
| Serine/threonine-protein kinase PIM2 | Kinase | 0.118883307 |
| Receptor protein-tyrosine kinase erbB-2 | Kinase | 0.118883307 |
| Histone deacetylase 3 | Eraser | 0.118883307 |
| Vasopressin V1a receptor | Family A G protein-coupled receptor | 0.118883307 |
| Histone deacetylase 2 | Eraser | 0.118883307 |
| Kappa Opioid receptor | Family A G protein-coupled receptor | 0.118883307 |
| Phosphodiesterase 3 | Phosphodiesterase | 0.118883307 |
| Phosphodiesterase 3B | Phosphodiesterase | 0.118883307 |
| Histone deacetylase 1 | Eraser | 0.118883307 |
| MAP kinase p38 beta | Kinase | 0.118883307 |
| Tyrosine-protein kinase BRK | Kinase | 0.118883307 |
| Sodium/glucose cotransporter 1 | Electrochemical transporter | 0.118883307 |
| Smoothened homolog | Frizzled family G protein-coupled receptor | 0.118883307 |
| Corticotropin releasing factor receptor 1 | Family B G protein-coupled receptor | 0.118883307 |
| Macrophage colony stimulating factor receptor (by homology) | Kinase | 0.118883307 |
| Ephrin type-A receptor 2 | Kinase | 0.118883307 |
| Protein farnesyltransferase | Enzyme | 0.118883307 |
| Interleukin-8 receptor B | Family A G protein-coupled receptor | 0.118883307 |
| Acetyl-CoA carboxylase 1 | Enzyme | 0.118883307 |
| Endothelin receptor ET-B | Family A G protein-coupled receptor | 0.118883307 |
 |
Table 16.
Glyburide.
| Target | Target Class | Probability* |
| Sulfonylurea receptor 2, Kir6.2 | Primary active transporter | 1 |
| Sulfonylurea receptor 1, Kir6.2 | Voltage-gated ion channel | 1 |
| Cytochrome P450 2C9 | Cytochrome P450 | 1 |
| Bile salt export pump | Primary active transporter | 1 |
| Sulfonylurea receptor 1 | Primary active transporter | 0.117389882 |
| Phosphoglycerate kinase 1 | Enzyme | 0.100634432 |
| Protein-tyrosine phosphatase 1B | Phosphatase | 0.100634432 |
| Purinergic receptor P2Y12 | Family A G protein-coupled receptor | 0.100634432 |
| Bromodomain-containing protein 4 | Reader | 0.100634432 |
| Orexin receptor 2 | Family A G protein-coupled receptor | 0.100634432 |
| Orexin receptor 1 | Family A G protein-coupled receptor | 0.100634432 |
| Nicotinamide phosphoribosyltransferase | Enzyme | 0.100634432 |
| Macrophage colony stimulating factor receptor | Kinase | 0.100634432 |
| Platelet-derived growth factor receptor beta | Kinase | 0.100634432 |
| Tyrosine-protein kinase receptor FLT3 | Kinase | 0.100634432 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.100634432 |
| Multidrug resistance-associated protein 1 | Primary active transporter | 0.100634432 |
| Cyclin-dependent kinase 2 | Kinase | 0.100634432 |
| P-glycoprotein 1 | Primary active transporter | 0.100634432 |
| Phosphodiesterase 10A (by homology) | Phosphodiesterase | 0.100634432 |
| Serine/threonine-protein kinase mTOR | Kinase | 0.100634432 |
| PI3-kinase p110-alpha subunit | Enzyme | 0.100634432 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.100634432 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.100634432 |
| Smoothened homolog | Frizzled family G protein-coupled receptor | 0.100634432 |
| Diacylglycerol O-acyltransferase 1 | Enzyme | 0.100634432 |
| Carbonic anhydrase II | Lyase | 0.100634432 |
| Tyrosine kinase non-receptor protein 2 | Kinase | 0.100634432 |
| Stem cell growth factor receptor | Kinase | 0.100634432 |
| 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 | Enzyme | 0.100634432 |
| ALK tyrosine kinase receptor | Kinase | 0.100634432 |
| Adenosine A1 receptor (by homology) | Family A G protein-coupled receptor | 0.100634432 |
| Adenosine A2a receptor (by homology) | Family A G protein-coupled receptor | 0.100634432 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Bile acid receptor FXR | Nuclear receptor | 0.100634432 |
| PI3-kinase p110-delta subunit | Enzyme | 0.100634432 |
| Thymidine kinase, mitochondrial | Enzyme | 0.100634432 |
| Acetyl-coenzyme A transporter 1 | Electrochemical transporter | 0.100634432 |
| Insulin receptor | Kinase | 0.100634432 |
| Hepatocyte growth factor receptor | Kinase | 0.100634432 |
| Carbonic anhydrase I | Lyase | 0.100634432 |
| Carbonic anhydrase XII | Lyase | 0.100634432 |
| Insulin-like growth factor I receptor | Kinase | 0.100634432 |
| Dual specificity mitogen-activated protein kinase kinase 1 | Kinase | 0.100634432 |
| N-acylsphingosine-amidohydrolase | Enzyme | 0.100634432 |
| Glucose-dependent insulinotropic receptor | Family A G protein-coupled receptor | 0.100634432 |
| CaM kinase II | Kinase | 0.100634432 |
| 5-lipoxygenase activating protein | Other cytosolic protein | 0.100634432 |
| Serine/threonine-protein kinase B-raf | Kinase | 0.100634432 |
| Protein Wnt-3a | Unclassified protein | 0.100634432 |
| Tyrosine-protein kinase JAK1 | Kinase | 0.100634432 |
| Tankyrase-2 | Enzyme | 0.100634432 |
| Prostanoid EP1 receptor | Family A G protein-coupled receptor | 0.100634432 |
| Tyrosine-protein kinase SYK | Kinase | 0.100634432 |
| Phosphodiesterase 4D | Phosphodiesterase | 0.100634432 |
| CDK8/Cyclin C | Kinase | 0.100634432 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.100634432 |
| Phosphodiesterase 9A | Phosphodiesterase | 0.100634432 |
| Acetyl-CoA carboxylase 2 | Ligase | 0.100634432 |
| Cell division protein kinase 8 | Kinase | 0.100634432 |
| c-Jun N-terminal kinase 1 | Kinase | 0.100634432 |
| c-Jun N-terminal kinase 3 | Kinase | 0.100634432 |
| Translocator protein (by homology) | Membrane receptor | 0.100634432 |
| Carbonic anhydrase IX | Lyase | 0.100634432 |
| Receptor protein-tyrosine kinase erbB-2 | Kinase | 0.100634432 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.100634432 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.100634432 |
| Serine/threonine-protein kinase PIM1 | Kinase | 0.100634432 |
| Dual-specificity tyrosine-phosphorylation regulated kinase 1A (by homology) | Kinase | 0.100634432 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.100634432 |
| Transmembrane domain-containing protein TMIGD3 | Unclassified protein | 0.100634432 |
| Dual specificty protein kinase CLK1 (by homology) | Kinase | 0.100634432 |
| Dual specificity protein kinase CLK3 (by homology) | Kinase | 0.100634432 |
| Dual-specificity tyrosine-phosphorylation regulated kinase 2 | Kinase | 0.100634432 |
| Calcium sensing receptor | Family C G protein-coupled receptor | 0.100634432 |
| Voltage-gated calcium channel alpha2/delta subunit 1 | Calcium channel auxiliary subunit alpha2delta family | 0.100634432 |
| Caspase-6 | Protease | 0.100634432 |
| Caspase-7 | Protease | 0.100634432 |
| Caspase-1 | Protease | 0.100634432 |
| Tyrosine-protein kinase ABL | Kinase | 0.100634432 |
| Cyclin-dependent kinase 2/cyclin E1 | Kinase | 0.100634432 |
| Mitogen-activated protein kinase kinase kinase 12 | Enzyme | 0.100634432 |
| Metabotropic glutamate receptor 1 | Family C G protein-coupled receptor | 0.100634432 |
| c-Jun N-terminal kinase 2 | Kinase | 0.100634432 |
| Steroidogenic factor 1 | Nuclear receptor | 0.100634432 |
| Eukaryotic translation initiation factor 2-alpha kinase 3 | Kinase | 0.100634432 |
| Tyrosine-protein kinase SRC | Kinase | 0.100634432 |
| DNA-dependent protein kinase | Kinase | 0.100634432 |
| Fibroblast growth factor receptor 2 | Kinase | 0.100634432 |
| Corticotropin releasing factor receptor 1 | Family B G protein-coupled receptor | 0.100634432 |
| Nerve growth factor receptor Trk-A | Kinase | 0.100634432 |
| PI3-kinase p110-beta subunit | Enzyme | 0.100634432 |
| PI3-kinase p110-gamma subunit | Enzyme | 0.100634432 |
| Serine/threonine-protein kinase Chk1 | Kinase | 0.100634432 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.100634432 |
| Interleukin-8 receptor B | Family A G protein-coupled receptor | 0.100634432 |
| Neuronal acetylcholine receptor protein alpha-7 subunit | Ligand-gated ion channel | 0.100634432 |
| CDK2/Cyclin A | Kinase | 0.100634432 |
| Hypoxia-inducible factor 1 alpha | Transcription factor | 0.100634432 |
| MAP kinase-activated protein kinase 2 | Kinase | 0.100634432 |
 |
Table 17.
Tolazamide.
| Target | Target Class | Probability* |
| P2X purinoceptor 7 | Ligand-gated ion channel | 0.097874534 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.097874534 |
| Melatonin receptor 1B | Family A G protein-coupled receptor | 0.097874534 |
| Cytochrome P450 19A1 | Cytochrome P450 | 0.097874534 |
| Glutathione transferase omega 1 | Enzyme | 0.097874534 |
| Vascular endothelial growth factor receptor 1 | Kinase | 0.097874534 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.097874534 |
| Prolyl endopeptidase | Protease | 0.097874534 |
| Orexin receptor 2 | Family A G protein-coupled receptor | 0.097874534 |
| Phosphatidylinositol-5-phosphate 4-kinase type-2 gamma | Enzyme | 0.097874534 |
| MAP kinase p38 alpha | Kinase | 0.097874534 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.097874534 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.097874534 |
| Orexin receptor 1 | Family A G protein-coupled receptor | 0.097874534 |
| Bromodomain-containing protein 4 | Reader | 0.097874534 |
| Bromodomain-containing protein 2 | Reader | 0.097874534 |
| Bromodomain-containing protein 3 | Reader | 0.097874534 |
| Cyclin-dependent kinase 2/cyclin E | Other cytosolic protein | 0.097874534 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.097874534 |
| Androgen Receptor | Nuclear receptor | 0.097874534 |
| Protoporphyrinogen oxidase | Oxidoreductase | 0.097874534 |
| Epoxide hydrolase 1 | Protease | 0.097874534 |
| Glycogen synthase kinase-3 beta | Kinase | 0.097874534 |
| Cyclin-dependent kinase 2 | Kinase | 0.097874534 |
| Hepatocyte growth factor receptor | Kinase | 0.097874534 |
| Nitric oxide synthase, inducible | Enzyme | 0.097874534 |
| Metabotropic glutamate receptor 5 (by homology) | Family C G protein-coupled receptor | 0.097874534 |
| Voltage-gated potassium channel subunit Kv1.3 | Voltage-gated ion channel | 0.097874534 |
| c-Jun N-terminal kinase 1 | Kinase | 0.097874534 |
| c-Jun N-terminal kinase 3 | Kinase | 0.097874534 |
| Glutaminyl-peptide cyclotransferase | Enzyme | 0.097874534 |
| Plectin | Unclassified protein | 0.097874534 |
| Adenosine A1 receptor | Family A G protein-coupled receptor | 0.097874534 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.097874534 |
| Beta-secretase 1 | Protease | 0.097874534 |
| Long-chain fatty acid transport protein 1 | Electrochemical transporter | 0.097874534 |
| Dopamine transporter | Electrochemical transporter | 0.097874534 |
| Beta secretase 2 | Protease | 0.097874534 |
| Protein kinase C gamma (by homology) | Kinase | 0.097874534 |
| ALK tyrosine kinase receptor | Kinase | 0.097874534 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.097874534 |
| Butyrylcholinesterase | Hydrolase | 0.097874534 |
| Cathepsin K | Protease | 0.097874534 |
| Glycogen synthase kinase-3 alpha | Kinase | 0.097874534 |
| Potassium channel subfamily K member 3 | Voltage-gated ion channel | 0.097874534 |
| Cyclin-dependent kinase 1/cyclin B | Other cytosolic protein | 0.097874534 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.097874534 |
| Cyclin-dependent kinase 4 | Kinase | 0.097874534 |
| Hydroxycarboxylic acid receptor 2 | Family A G protein-coupled receptor | 0.097874534 |
| Insulin-like growth factor I receptor | Kinase | 0.097874534 |
| Transthyretin | Secreted protein | 0.097874534 |
| NAD-dependent deacetylase sirtuin 1 | Eraser | 0.097874534 |
| Tyrosine-protein kinase JAK3 | Kinase | 0.097874534 |
| C5a anaphylatoxin chemotactic receptor | Family A G protein-coupled receptor | 0.097874534 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.097874534 |
| Protein tyrosine kinase 2 beta | Kinase | 0.097874534 |
| ADAMTS5 | Protease | 0.097874534 |
| ADAMTS4 | Protease | 0.097874534 |
| Matrix metalloproteinase 3 | Protease | 0.097874534 |
| ADAM17 | Protease | 0.097874534 |
| Prostanoid EP2 receptor | Family A G protein-coupled receptor | 0.097874534 |
| Progesterone receptor | Nuclear receptor | 0.097874534 |
| SUMO-activating enzyme | Enzyme | 0.097874534 |
| Inosine-5’-monophosphate dehydrogenase 2 | Oxidoreductase | 0.097874534 |
| Tyrosine-protein kinase SYK | Kinase | 0.097874534 |
| Cathepsin (B and K) | Protease | 0.097874534 |
| Estrogen receptor beta | Nuclear receptor | 0.097874534 |
| Nerve growth factor receptor Trk-A | Kinase | 0.097874534 |
| Cathepsin S | Protease | 0.097874534 |
| Fibroblast growth factor receptor 1 | Kinase | 0.097874534 |
| Hexokinase type IV | Enzyme | 0.097874534 |
| Estrogen receptor alpha | Nuclear receptor | 0.097874534 |
| Anandamide amidohydrolase | Enzyme | 0.097874534 |
| Cathepsin (V and K) (by homology) | Protease | 0.097874534 |
| c-Jun N-terminal kinase 2 | Kinase | 0.097874534 |
| Arylamine N-acetyltransferase 1 | Enzyme | 0.097874534 |
| Cholecystokinin A receptor | Family A G protein-coupled receptor | 0.097874534 |
| Platelet-derived growth factor receptor beta | Kinase | 0.097874534 |
| GABA receptor alpha-1 subunit | Ligand-gated ion channel | 0.097874534 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.097874534 |
| Platelet activating factor receptor | Family A G protein-coupled receptor | 0.097874534 |
| Phosphodiesterase 4B | Phosphodiesterase | 0.097874534 |
| Cholecystokinin B receptor | Family A G protein-coupled receptor | 0.097874534 |
| Voltage-gated L-type calcium channel alpha-1C subunit | Voltage-gated ion channel | 0.097874534 |
| Induced myeloid leukemia cell differentiation protein Mcl-1 | Other cytosolic protein | 0.097874534 |
| Serotonin transporter | Electrochemical transporter | 0.097874534 |
| Serine/threonine-protein kinase Chk2 | Kinase | 0.097874534 |
| Liver glycogen phosphorylase | Enzyme | 0.097874534 |
| Serine/threonine-protein kinase PLK4 | Kinase | 0.097874534 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.097874534 |
| Serine/threonine-protein kinase RIPK2 | Kinase | 0.097874534 |
| Isocitrate dehydrogenase [NADP] cytoplasmic | Enzyme | 0.097874534 |
| Potassium channel subfamily K member 9 | Voltage-gated ion channel | 0.097874534 |
| Tyrosine-protein kinase SRC | Kinase | 0.097874534 |
| Focal adhesion kinase 1 | Kinase | 0.097874534 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.097874534 |
| MAP kinase-interacting serine/threonine-protein kinase MNK1 | Kinase | 0.097874534 |
| Tankyrase-2 | Enzyme | 0.097874534 |
| Glucagon-like peptide 1 receptor | Family B G protein-coupled receptor | 0.097874534 |
| Stem cell growth factor receptor | Kinase | 0.097874534 |
 |
Table 18.
Tolbutamide.
| Target | Target Class | Probability* |
| Fructose-1,6-bisphosphatase | Enzyme | 0.098947479 |
| Carbonic anhydrase II | Lyase | 0.071715932 |
| Carbonic anhydrase I | Lyase | 0.071715932 |
| Carbonic anhydrase XII | Lyase | 0.071715932 |
| Carbonic anhydrase IX | Lyase | 0.071715932 |
| Adenosine A1 receptor | Family A G protein-coupled receptor | 0.053556076 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.053556076 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.053556076 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.053556076 |
| P2X purinoceptor 7 | Ligand-gated ion channel | 0.053556076 |
| MAP kinase p38 alpha | Kinase | 0.053556076 |
| NAD-dependent protein deacylase sirtuin-5, mitochondrial | Eraser | 0.053556076 |
| NAD-dependent deacetylase sirtuin 2 | Eraser | 0.053556076 |
| NAD-dependent deacetylase sirtuin 1 | Eraser | 0.053556076 |
| Orexin receptor 2 | Family A G protein-coupled receptor | 0.053556076 |
| Orexin receptor 1 | Family A G protein-coupled receptor | 0.053556076 |
| Cyclin-dependent kinase 2/cyclin E | Other cytosolic protein | 0.053556076 |
| Cyclin-dependent kinase 1/cyclin B | Other cytosolic protein | 0.053556076 |
| Estrogen receptor beta | Nuclear receptor | 0.053556076 |
| Cytochrome P450 19A1 | Cytochrome P450 | 0.053556076 |
| Cathepsin K | Protease | 0.053556076 |
| Cathepsin S | Protease | 0.053556076 |
| Tyrosine-protein kinase ITK/TSK | Kinase | 0.053556076 |
| Glutathione transferase omega 1 | Enzyme | 0.053556076 |
| Cathepsin (V and K) (by homology) | Protease | 0.053556076 |
| Glutaminyl-peptide cyclotransferase | Enzyme | 0.053556076 |
| G-protein coupled receptor kinase 2 | Kinase | 0.053556076 |
| Tyrosine-protein kinase JAK3 | Kinase | 0.053556076 |
| Nerve growth factor receptor Trk-A | Kinase | 0.053556076 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.053556076 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.053556076 |
| Arachidonate 5-lipoxygenase | Oxidoreductase | 0.053556076 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.053556076 |
| Metabotropic glutamate receptor 5 (by homology) | Family C G protein-coupled receptor | 0.053556076 |
| Fibroblast growth factor receptor 1 | Kinase | 0.053556076 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.053556076 |
| Cyclin-dependent kinase 2 | Kinase | 0.053556076 |
| Signal transducer and activator of transcription 5B | Transcription factor | 0.053556076 |
| Bromodomain-containing protein 4 | Reader | 0.053556076 |
| Bromodomain-containing protein 2 | Reader | 0.053556076 |
| Phenylalanyl-tRNA synthetase mitochondrial | Enzyme | 0.053556076 |
| Androgen Receptor | Nuclear receptor | 0.053556076 |
| Heat shock protein HSP 90-alpha | Other cytosolic protein | 0.053556076 |
| Inosine-5’-monophosphate dehydrogenase 2 | Oxidoreductase | 0.053556076 |
| Insulin-like growth factor I receptor | Kinase | 0.053556076 |
| Fatty acid desaturase 1 | Enzyme | 0.053556076 |
| Endothelin receptor ET-A (by homology) | Family A G protein-coupled receptor | 0.053556076 |
| Induced myeloid leukemia cell differentiation protein Mcl-1 | Other cytosolic protein | 0.053556076 |
| Protein tyrosine kinase 2 beta | Kinase | 0.053556076 |
| Nuclear receptor subfamily 4 group A member 1 | Nuclear receptor | 0.053556076 |
| Glucagon-like peptide 1 receptor | Family B G protein-coupled receptor | 0.053556076 |
| Integrin alpha-4/beta-7 | Membrane receptor | 0.053556076 |
| c-Jun N-terminal kinase 1 | Kinase | 0.053556076 |
| c-Jun N-terminal kinase 3 | Kinase | 0.053556076 |
| c-Jun N-terminal kinase 2 | Kinase | 0.053556076 |
| Arylamine N-acetyltransferase 1 | Enzyme | 0.053556076 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.053556076 |
| Dual-specificity tyrosine-phosphorylation regulated kinase 1A (by homology) | Kinase | 0.053556076 |
| MAP kinase-activated protein kinase 2 | Kinase | 0.053556076 |
| Cyclin-dependent kinase 1 | Kinase | 0.053556076 |
| Tyrosine-protein kinase TYK2 | Kinase | 0.053556076 |
| Cathepsin (B and K) | Protease | 0.053556076 |
| Plectin | Unclassified protein | 0.053556076 |
| Prostanoid EP2 receptor | Family A G protein-coupled receptor | 0.053556076 |
| Epoxide hydrolase 1 | Protease | 0.053556076 |
| Protein farnesyltransferase | Enzyme | 0.053556076 |
| Tyrosine-protein kinase LCK | Kinase | 0.053556076 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.053556076 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.053556076 |
| Cyclin-dependent kinase 2/cyclin E1 | Kinase | 0.053556076 |
| Tyrosine-protein kinase receptor FLT3 | Kinase | 0.053556076 |
| Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET | Kinase | 0.053556076 |
| Fibroblast growth factor receptor 3 | Kinase | 0.053556076 |
| Phosphodiesterase 10A | Phosphodiesterase | 0.053556076 |
| Muscle, skeletal receptor tyrosine protein kinase | Kinase | 0.053556076 |
| Cyclin-dependent kinase 2/cyclin A | Other cytosolic protein | 0.053556076 |
| Glycogen synthase kinase-3 beta | Kinase | 0.053556076 |
| Tyrosine-protein kinase SRC | Kinase | 0.053556076 |
| Cholecystokinin B receptor | Family A G protein-coupled receptor | 0.053556076 |
| Hormone sensitive lipase | Enzyme | 0.053556076 |
| Tankyrase-2 | Enzyme | 0.053556076 |
| Amine oxidase, copper containing | Enzyme | 0.053556076 |
| Voltage-gated L-type calcium channel alpha-1C subunit | Voltage-gated ion channel | 0.053556076 |
| Estrogen receptor alpha | Nuclear receptor | 0.053556076 |
| Cathepsin D | Protease | 0.053556076 |
| Hexokinase type IV | Enzyme | 0.053556076 |
| Cathepsin L | Protease | 0.053556076 |
| MAP kinase-interacting serine/threonine-protein kinase MNK1 | Kinase | 0.053556076 |
| Bromodomain-containing protein 3 | Reader | 0.053556076 |
| Monoamine oxidase B | Oxidoreductase | 0.053556076 |
| GABA-A receptor; alpha-5/beta-3/gamma-2 | Ligand-gated ion channel | 0.053556076 |
| Ephrin receptor | Kinase | 0.053556076 |
| Axin1/beta-catenin | Unclassified protein | 0.053556076 |
| Vascular endothelial growth factor receptor 3 | Kinase | 0.053556076 |
| ADAMTS5 | Protease | 0.053556076 |
| Phosphorylase kinase gamma subunit 2 | Kinase | 0.053556076 |
| Tyrosine-protein kinase SYK | Kinase | 0.053556076 |
| Focal adhesion kinase 1 | Kinase | 0.053556076 |
| Mitogen-activated protein kinase kinase kinase 9 | Kinase | 0.053556076 |
| ALK tyrosine kinase receptor | Kinase | 0.053556076 |
 |
Table 19.
Gliclazide.
| Target | Target Class | Probability* |
| Phosphodiesterase 10A | Phosphodiesterase | 0.111501865 |
| P2X purinoceptor 7 | Ligand-gated ion channel | 0.111501865 |
| Cytochrome P450 19A1 | Cytochrome P450 | 0.111501865 |
| Bromodomain-containing protein 4 | Reader | 0.111501865 |
| Tyrosine-protein kinase JAK2 | Kinase | 0.111501865 |
| Matrix metalloproteinase 9 | Protease | 0.111501865 |
| Matrix metalloproteinase 2 | Protease | 0.111501865 |
| Matrix metalloproteinase 14 | Protease | 0.111501865 |
| Adenosine A2a receptor | Family A G protein-coupled receptor | 0.111501865 |
| Adenosine A2b receptor | Family A G protein-coupled receptor | 0.111501865 |
| Metabotropic glutamate receptor 5 (by homology) | Family C G protein-coupled receptor | 0.111501865 |
| Butyrylcholinesterase | Hydrolase | 0.111501865 |
| Adenosine A1 receptor (by homology) | Family A G protein-coupled receptor | 0.111501865 |
| Protein tyrosine kinase 2 beta | Kinase | 0.111501865 |
| Androgen Receptor | Nuclear receptor | 0.111501865 |
| Epoxide hydrolase 1 | Protease | 0.111501865 |
| MAP kinase p38 alpha | Kinase | 0.111501865 |
| Melatonin receptor 1B | Family A G protein-coupled receptor | 0.111501865 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.111501865 |
| Cathepsin (B and K) | Protease | 0.111501865 |
| Orexin receptor 2 | Family A G protein-coupled receptor | 0.111501865 |
| Orexin receptor 1 | Family A G protein-coupled receptor | 0.111501865 |
| Glutathione transferase omega 1 | Enzyme | 0.111501865 |
| Hepatocyte growth factor receptor | Kinase | 0.111501865 |
| Glutaminyl-peptide cyclotransferase | Enzyme | 0.111501865 |
| Bromodomain-containing protein 2 | Reader | 0.111501865 |
| Bromodomain-containing protein 3 | Reader | 0.111501865 |
| Tyrosine-protein kinase JAK3 | Kinase | 0.111501865 |
| Serine/threonine-protein kinase Aurora-B | Kinase | 0.111501865 |
| Cathepsin K | Protease | 0.111501865 |
| Nerve growth factor receptor Trk-A | Kinase | 0.111501865 |
| Cathepsin S | Protease | 0.111501865 |
| Cyclin-dependent kinase 2 | Kinase | 0.111501865 |
| GABA receptor alpha-5 subunit | Ligand-gated ion channel | 0.111501865 |
| Cyclin-dependent kinase 5/CDK5 activator 1 | Kinase | 0.111501865 |
| Cathepsin (V and K) | Protease | 0.111501865 |
| Cathepsin L | Protease | 0.111501865 |
| Nitric oxide synthase, inducible | Enzyme | 0.111501865 |
| NAD-dependent deacetylase sirtuin 1 | Eraser | 0.111501865 |
| Cyclin-dependent kinase 2/cyclin E | Other cytosolic protein | 0.111501865 |
| Glycogen synthase kinase-3 beta | Kinase | 0.111501865 |
| Poly [ADP-ribose] polymerase-1 | Enzyme | 0.111501865 |
| Cyclin-dependent kinase 4 | Kinase | 0.111501865 |
| Cathepsin G | Protease | 0.111501865 |
| Tankyrase-2 | Enzyme | 0.111501865 |
| Serine/threonine-protein kinase Aurora-A | Kinase | 0.111501865 |
| Vascular endothelial growth factor receptor 1 | Kinase | 0.111501865 |
| Cyclin-dependent kinase 2/cyclin E1 | Kinase | 0.111501865 |
| Tyrosine-protein kinase receptor FLT3 | Kinase | 0.111501865 |
| Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET | Kinase | 0.111501865 |
| GABA-A receptor; alpha-5/beta-3/gamma-2 | Ligand-gated ion channel | 0.111501865 |
| Tyrosine-protein kinase LCK | Kinase | 0.111501865 |
| Fibroblast growth factor receptor 3 | Kinase | 0.111501865 |
| Vascular endothelial growth factor receptor 2 | Kinase | 0.111501865 |
| Prolyl endopeptidase | Protease | 0.111501865 |
| Muscle, skeletal receptor tyrosine protein kinase | Kinase | 0.111501865 |
| Phosphodiesterase 5A | Phosphodiesterase | 0.111501865 |
| Dopamine transporter | Electrochemical transporter | 0.111501865 |
| Beta amyloid A4 protein | Membrane receptor | 0.111501865 |
| Beta secretase 2 | Protease | 0.111501865 |
| Beta-secretase 1 | Protease | 0.111501865 |
| c-Jun N-terminal kinase 1 | Kinase | 0.111501865 |
| c-Jun N-terminal kinase 3 | Kinase | 0.111501865 |
| Insulin-like growth factor I receptor | Kinase | 0.111501865 |
| Insulin receptor | Kinase | 0.111501865 |
| Phosphodiesterase 4B | Phosphodiesterase | 0.111501865 |
| Phosphodiesterase 7A | Phosphodiesterase | 0.111501865 |
| Fibroblast growth factor receptor 1 | Kinase | 0.111501865 |
| Cyclin-dependent kinase 1/cyclin B | Other cytosolic protein | 0.111501865 |
| Dual-specificity tyrosine-phosphorylation regulated kinase 1A (by homology) | Kinase | 0.111501865 |
| Arachidonate 5-lipoxygenase | Oxidoreductase | 0.111501865 |
| Tyrosine-protein kinase SRC | Kinase | 0.111501865 |
| Signal transducer and activator of transcription 5B | Transcription factor | 0.111501865 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.111501865 |
| Inosine-5’-monophosphate dehydrogenase 2 | Oxidoreductase | 0.111501865 |
| SUMO-activating enzyme | Enzyme | 0.111501865 |
| Anandamide amidohydrolase | Enzyme | 0.111501865 |
| Hydroxycarboxylic acid receptor 2 | Family A G protein-coupled receptor | 0.111501865 |
| Induced myeloid leukemia cell differentiation protein Mcl-1 | Other cytosolic protein | 0.111501865 |
| Sodium channel protein type V alpha subunit | Voltage-gated ion channel | 0.111501865 |
| Long-chain fatty acid transport protein 1 | Electrochemical transporter | 0.111501865 |
| Alpha-1d adrenergic receptor | Family A G protein-coupled receptor | 0.111501865 |
| Alpha-1a adrenergic receptor | Family A G protein-coupled receptor | 0.111501865 |
| Tyrosine-protein kinase SYK | Kinase | 0.111501865 |
| Serine/threonine-protein kinase PLK1 | Kinase | 0.111501865 |
| Serine/threonine-protein kinase PLK2 | Kinase | 0.111501865 |
| Cholecystokinin A receptor | Family A G protein-coupled receptor | 0.111501865 |
| C5a anaphylatoxin chemotactic receptor | Family A G protein-coupled receptor | 0.111501865 |
| Cholecystokinin B receptor | Family A G protein-coupled receptor | 0.111501865 |
| Potassium channel subfamily K member 3 | Voltage-gated ion channel | 0.111501865 |
| Potassium channel subfamily K member 9 | Voltage-gated ion channel | 0.111501865 |
| Peroxisome proliferator-activated receptor gamma | Nuclear receptor | 0.111501865 |
| Estrogen receptor beta | Nuclear receptor | 0.111501865 |
| Tumor necrosis factor receptor R1 | Membrane receptor | 0.111501865 |
| Nuclear receptor subfamily 4 group A member 1 | Nuclear receptor | 0.111501865 |
| Platelet activating factor receptor | Family A G protein-coupled receptor | 0.111501865 |
| ADAMTS5 | Protease | 0.111501865 |
| Serotonin transporter | Electrochemical transporter | 0.111501865 |
| ADAMTS4 | Protease | 0.111501865 |
| Leukocyte elastase | Protease | 0.111501865 |
Group 7. Thiazolidinediones and Target Predictions with Artificial Intelligence. This class of antidiabetic agents increases insulin sensitivity by acting on adipose, muscle and liver, in a lesser extent, to increase glucose utilization and decrease glucose production. Two thiazolidinediones are currently available (59.8% to 66.5% main target prediction).
 |
Table 20.
Rosiglitazone.
| Target | Target Class | Probability* |
| Peroxisome proliferator-activated receptor gamma | Nuclear receptor | 1 |
| Thromboxane-A synthase | Cytochrome P450 | 0.843606914 |
| Monoamine oxidase B | Oxidoreductase | 0.843606914 |
| Carbonic anhydrase II | Lyase | 0.843606914 |
| Type-1 angiotensin II receptor (by homology) | Family A G protein-coupled receptor | 0.843606914 |
| Peroxisome proliferator-activated receptor alpha | Nuclear receptor | 0.843606914 |
| Peroxisome proliferator-activated receptor delta | Nuclear receptor | 0.843606914 |
| Bile salt export pump | Primary active transporter | 0.843606914 |
| Free fatty acid receptor 1 | Family A G protein-coupled receptor | 0.097239989 |
| 15-hydroxyprostaglandin dehydrogenase [NAD+] | Enzyme | 0.097239989 |
| Matrix metalloproteinase 8 | Protease | 0.097239989 |
| Phospholipase A2 group IIA | Enzyme | 0.097239989 |
| Macrophage colony stimulating factor receptor | Kinase | 0.097239989 |
| Matrix metalloproteinase 3 | Protease | 0.097239989 |
| Glucocorticoid receptor | Nuclear receptor | 0.097239989 |
| Tyrosine-protein kinase LCK | Kinase | 0.097239989 |
| Ileal bile acid transporter | Electrochemical transporter | 0.097239989 |
| Prostanoid DP receptor | Family A G protein-coupled receptor | 0.097239989 |
| Cyclin-dependent kinase 9 | Kinase | 0.097239989 |
| Calpain 1 | Protease | 0.097239989 |
| Calpain 2 | Protease | 0.097239989 |
| MAP kinase p38 alpha | Kinase | 0.097239989 |
| Methionyl-tRNA synthetase | Enzyme | 0.097239989 |
| Dihydroorotate dehydrogenase | Oxidoreductase | 0.097239989 |
| Endothelin receptor ET-A | Family A G protein-coupled receptor | 0.097239989 |
| Epoxide hydratase | Protease | 0.097239989 |
| Hydroxycarboxylic acid receptor 2 | Family A G protein-coupled receptor | 0.097239989 |
| Lysine-specific demethylase 4C | Eraser | 0.097239989 |
| Protein-tyrosine phosphatase 1B | Phosphatase | 0.097239989 |
 |
Table 21.
Pioglitazone.HCl.
| Target | Target Class | Probability* |
| Monoamine oxidase B | Oxidoreductase | 0.938790203 |
| Carbonic anhydrase II | Lyase | 0.938790203 |
| Peroxisome proliferator-activated receptor gamma | Nuclear receptor | 0.938790203 |
| Peroxisome proliferator-activated receptor alpha | Nuclear receptor | 0.938790203 |
| Bile salt export pump | Primary active transporter | 0.938790203 |
| Thromboxane-A synthase | Cytochrome P450 | 0.097239989 |
| Type-1 angiotensin II receptor (by homology) | Family A G protein-coupled receptor | 0.097239989 |
| Peroxisome proliferator-activated receptor delta | Nuclear receptor | 0.097239989 |
| 15-hydroxyprostaglandin dehydrogenase [NAD+] | Enzyme | 0.097239989 |
| Free fatty acid receptor 1 | Family A G protein-coupled receptor | 0.097239989 |
| Macrophage colony stimulating factor receptor | Kinase | 0.097239989 |
| Vanilloid receptor | Voltage-gated ion channel | 0.097239989 |
| Dihydroorotate dehydrogenase | Oxidoreductase | 0.097239989 |
| Epoxide hydratase | Protease | 0.097239989 |
| Hexokinase type IV | Enzyme | 0.097239989 |
| Bombesin receptor subtype-3 | Family A G protein-coupled receptor | 0.097239989 |
| Phosphodiesterase 10A (by homology) | Phosphodiesterase | 0.097239989 |
| Adenosine A3 receptor | Family A G protein-coupled receptor | 0.097239989 |
| Cyclin-dependent kinase 9 | Kinase | 0.097239989 |
| Alpha-2b adrenergic receptor | Family A G protein-coupled receptor | 0.097239989 |
| Epidermal growth factor receptor erbB1 | Kinase | 0.097239989 |
| Norepinephrine transporter | Electrochemical transporter | 0.097239989 |
| Glycogen synthase kinase-3 beta | Kinase | 0.097239989 |
| Induced myeloid leukemia cell differentiation protein Mcl-1 | Other cytosolic protein | 0.097239989 |
| Adenosine A1 receptor | Family A G protein-coupled receptor | 0.097239989 |
| Tyrosine-protein kinase LCK | Kinase | 0.097239989 |
| Ileal bile acid transporter | Electrochemical transporter | 0.097239989 |
| Receptor protein-tyrosine kinase erbB-2 | Kinase | 0.097239989 |
| Beta-3 adrenergic receptor | Family A G protein-coupled receptor | 0.097239989 |
| Cytochrome P450 3A4 | Cytochrome P450 | 0.097239989 |
| Phospholipase A2 group IIA | Enzyme | 0.097239989 |
| Cathepsin (V and K) | Protease | 0.097239989 |
| Cathepsin L | Protease | 0.097239989 |
| Aldo-keto-reductase family 1 member C3 | Enzyme | 0.097239989 |
| Caspase-3 | Protease | 0.097239989 |
| MAP kinase p38 alpha | Kinase | 0.097239989 |
| Caspase-6 | Protease | 0.097239989 |
| Caspase-7 | Protease | 0.097239989 |
| Caspase-8 | Protease | 0.097239989 |
| Ghrelin receptor | Family A G protein-coupled receptor | 0.097239989 |
| Apoptosis regulator Bcl-X | Other ion channel | 0.097239989 |
| Apoptosis regulator Bcl-2 | Other ion channel | 0.097239989 |
| Caspase-2 | Protease | 0.097239989 |
Molecules or natural substances in the body are target specific receptors on the surface of cells. It substances bind with the receptor on a cell and stimulate the receptor to perform its function, which is to produce or to inhibit a specific action in the cell. Antidiabetic agents can also target and bind with these receptors. Then this drugs act as agonists, stimulating the receptor in the same way that the body’s natural substances do. Others act as antagonists, blocking the action of the natural substance on the receptor. Each type of receptor has many subtypes, and this antidiabetic drugs may act on one or several subtypes of receptors [33].
Expectance and Conclusions
Polypharmacy is widespread among older people with diabetes and exists evidence for an association between polypharmacy and many adverse outcomes, including adverse drug events and disability [34]. Doses of drugs in Elderly polypharmacy varies with ailments, age, sex and weight. With increasing age there is an increased prevalence of disease for which medication may be indicated and increased drug toxicity [35]. Drug toxicity in old age is influenced by changes in the quantity, affinity and responsiveness of drug targets, physiological reserve and response to injury. Drug-induced liver injury (DILI) is an important cause of hospitalization and of medication deregistration [36]. However, The World Health Organization (WHO) has listed 525 different drugs, that can lead to acute pancreatitis cases, as a medication side-effect [37].
Oral antidiabetic agents work in various ways to reduce blood sugar levels in people with type 2 diabetes. Some stimulate pancreatic insulin secretion, others improve the responsiveness of cells to insulin or prevent glucose production by the liver, while other groups inhibit or slow down glucose absorption after meals. However, previous experience has allowed us to formulate recommendations for the use of some groups of antidiabetic agents in diabetic patients. It is pertinent to highlight that it should not be forgotten that the selection of medications with high therapeutics effects and low cost is of paramount importance for patients that take medicine for a longer period and whose lives depend on it. This is an invaluable information for the maximization of antidiabetic agents for the benefit of the patients.
Declarations
Ethics approval and consent to participate: Not applicable
Consent for publication
As any identifiable information (image, face, name etc.) of participant is not revealed in the submission, for that Consent is not applicable.
Availability of data and material
All data generated or analyzed during this study are included in this published article. Besides, any additional data/files may be obtained from the corresponding author. Conflict of interests: The authors declare that there are no conflicts of interests.
Funding
This research received no specific grant from any funding agency in the public, commercial, private, or not-for-profit sectors.
Acknowledgments
We thank Dr. Cyril Ndidi Nwoye Nnamezie, an expert translator and native English speaker, a researcher in Medical Science and a physician by profession. The authors express their profound gratitude to the National Institute of Pediatrics (NIP) for the support in the publication of this article issued on the Program A022. Our special thanks to the Swiss National Science Foundation for scientific developments and to the Swiss Institute of Bioinformatics (SIB) for the creation and maintenance of the Web tools. SIB Molecular Modelling Group develop the Swiss Drug Design project. Swiss target prediction is operated by the Molecular Modelling Group of the SIB and the University of Lausanne.
Authors’ information
All participating authors are qualified as medical science researcher, recognized by the Health Ministry of Mexico.
References
- Solovyev, N.; Vanhaecke, F.; Michalke, B. Selenium and iodine in diabetes mellitus with a focus on the interplay and speciation of the elements. J. Trace Elem. Med. Biol. 2019, 56, 69–80. [Google Scholar] [CrossRef]
- Bjørklund, G.; Dadar, M.; Pivina, L.; Doşa, M.D.; Semenova, Y.; Aaseth, J. The role of zinc and copper in insulin resistance and diabetes mellitus. Curr. Med. Chem. 2019. [Google Scholar] [CrossRef]
- Heinrich Holzgreve. Treatment of hypertensive type 2 diabetics: Too late, too Little. Herz 2008, 33, 191–195. [Google Scholar] [CrossRef]
- Sobczak, A.I.S.; Stefanowicz, F.; Pitt, S.J.; Ajjan, R.A.; Stewart, A.J. Total plasma magnesium, zinc, copper and selenium concentrations in type-I and type-II diabetes. Biometals 2019, 32, 123–138. [Google Scholar] [CrossRef]
- Mahnaz Norouzi; Shaghayegh Norouzi; Alistaire Ruggiero; Mohammad S. Khan; Stephen Myers; Kylie Kavanagh; Ravichandra Vemuri. Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection. Microorganisms 2021, 9, 1211. [CrossRef]
- Wan-Xia Ma; Xing-Wu Ran. The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020, 51, 146–150. [CrossRef]
- Jeffrey, I. Mechanick; Elena, A. Christofides; Albert, E. Marchetti; Kristin, K. Hoddy; Jim Joachim; Refaat Hegazi; Osama Hamdy. The syndromic triad of COVID-19, type 2 diabetes, and malnutrition. Front. Nutr. 2023, 10, 1122203. [Google Scholar] [CrossRef]
- Noyola, D.E.; Hermosillo-Arredondo, N.; Ramírez-Juárez, C.; Werge-Sánchez, A. Association between obesity and diabetes prevalence and COVID-19 mortality in Mexico: An ecological study. J. Infect. Dev. Ctries. 2021, 15, 1396–1403. [Google Scholar] [CrossRef] [PubMed]
- Alcalde-Rabanal, J.E.; Orozco-Núñez, E.; Espinosa-Henao, O.E.; Arredondo-López, A.; Alcayde-Barranco, L. The complex scenario of obesity, diabetes and hypertension in the area of influence of primary healthcare facilities in Mexico. PLoS ONE. 2018, 13, e0187028. [Google Scholar] [CrossRef] [PubMed]
- Amira Mohammed Ali; Hiroshi Kunugi. Approaches to Nutritional Screening in Patients with Coronavirus Disease 2019 (COVID-19). Int. J. Environ. Res. Public Health. 2021, 18, 2772. [CrossRef]
- Graydon, S. Meneilly; Daniel, M. Tessier. Diabetes, Dementia and Hypoglycemia. Can. J. Diabetes. 2016, 40, 73–76. [Google Scholar] [CrossRef]
- Pont, C.; Ascaso, F.J.; Grzybowski, A.; Huerva, V. Corneal endothelial cell density during diabetes mellitus and ocular diabetes complications treatment. J. Fr. Ophtalmol. 2020, 43, 794–798. [Google Scholar] [CrossRef]
- Hébuterne, X.; Lemarié, E.; Michallet, M.; Beauvillain de Montreuil, C.; Schneider, S.M.; Goldwasser, F. Prevalence of malnutrition and current use of nutrition support in patients with cancer. J. Parenter Enteral Nutr. 2014, 38, 196–204. [Google Scholar] [CrossRef]
- Contreras, F.; Rivera, M.; Vasquez, J.; De la Parte, M.A.; Velasco, M. Diabetes and hypertension physiopathology and therapeutics. J. Hum. Hypertens. 2000, 14 (Suppl. S1), S26–S31. [Google Scholar] [CrossRef] [PubMed]
- Musso, C.G.; Macías Núñez, J.F. Feed-back between geriatric syndromes: General system theory in geriatrics. Int. Urol. Nephrol. 2006, 38, 785–786. [Google Scholar] [CrossRef] [PubMed]
- Bourke, R.; Doody, P.; Pérez, S.; Moloney, D.; Lipsitz, L.A.; Kenny, R.A. Cardiovascular Disorders and Falls Among Older Adults: A Systematic Review and Meta-Analysis. J. Gerontol. A Biol. Sci. Med. Sci. 2024, 79, glad221. [Google Scholar] [CrossRef] [PubMed]
- Dovjak, P. Frailty in older adults with heart disease. Z. Gerontol. Geriatr. 2022, 55, 465–470. [Google Scholar] [CrossRef]
- Masuzaki, H.; Kozuka, C.; Okamoto, S.; Yonamine, M.; Tanaka, H.; Shimabukuro, M. Brown rice-specific γ-oryzanol as a promising prophylactic avenue to protect against diabetes mellitus and obesity in humans. J. Diabetes Investig. 2019, 10, 18–25. [Google Scholar] [CrossRef]
- Mazhar Hussain; Asim Elahi; Abid Hussain; Javed Iqbal; Lubna Akhtar; Abdul Majid. Sodium-Glucose Cotransporter-2 (SGLT-2) Attenuates Serum Uric Acid (SUA) Level in Patients with Type 2 Diabetes. J. Diabetes Res. 2021, 9973862. [CrossRef]
- Wanrooy, B.J.; Kumar, K.P.; Wen, S.W.; Qin, C.X.; Ritchie, R.H.; Wong, C.H.Y. Distinct contributions of hyperglycemia and high-fat feeding in metabolic syndrome-induced neuroinflammation. J. Neuroinflammation. 2018, 15, 293. [Google Scholar] [CrossRef]
- Camargo, R.L.; Torrezan, R.; de Oliveira, J.C.; Branco, R.C.; Barella, L.F.; Grassiolli, S.; Gravena, C.; Mathias, P.C. An increase in glucose concentration in the lateral ventricles of the brain induces changes in autonomic nervous system activity. Neurol Res. 2013, 35, 15–21. [Google Scholar] [CrossRef]
- Yehuda Handelsman. Rationale for the Early Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Type 2 Diabetes. Adv. Ther. 2019, 36, 2567–2586. [Google Scholar] [CrossRef]
- Pratchayasakul, W.; Thongnak, L.O.; Chattipakorn, K.; Lungaphin, A.; Pongchaidecha, A.; Satjaritanun, P.; Jaiwongkam, T.; Kerdphoo, S.; Chattipakorn, S.C. Atorvastatin and insulin equally mitigate brain pathology in diabetic rats. Toxicol. Appl. Pharmacol. 2018, 342, 79–85. [Google Scholar] [CrossRef]
- Halliwell, B.; Gutteridge, J.M.C.; Cross, C.E. Free radicals, antioxidants, and human disease: Where are we now? J. Lab. Clin. Med. 1992, 119, 598–620. [Google Scholar] [PubMed]
- Niels, B. Dalsgaard; Lærke, S. Gasbjerg; Laura, S. Hansen; Nina, L. Hansen; Signe Stensen; Bolette Hartmann; Jens, F. Rehfeld; Jens, J. Holst; Tina Vilsbøll, Filip, K. Knop. The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes. Eur. J. Endocrinol. 2021, 184, 383–394. [Google Scholar] [CrossRef]
- David, M. Nathan; John, M. Lachin; Ionut Bebu; Henry, B. Burch; John, B. Buse; Andrea, L. Cherrington; Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes. N. Engl. J. Med. 2022, 387, 1075–1088. [Google Scholar] [CrossRef]
- Ke-Hung Chien; Ke-Hao Huang; Chi-Hsiang Chung; Yun-Hsiu Hsieh; Chang-Min Liang; Yu-Hua Chang; Tzu-Heng Weng; Wu-Chien Chien. The impact of diabetes mellitus medication on the incidence of endogenous endophthalmitis. PLoS ONE. 2020, 15, e0227442. [CrossRef]
- Iu, V. Lapina; O, Iu Narusov; V, Iu Mareev; Bolotina, M.G.; Shestakova, M.V.; Masenko, V.P.; Litonova, G.N.; Arzamastseva, N.E.; Baklanova, N.A.; Iu, N. Belenkov. Efficacy and safety of the use of metformin in patients with chronic heart failure and type 2 diabetes mellitus. Results of the study “rational effective mulicomponent therapy in the battle against diabetes mellitus in patients with chronic heart failure”. Kardiologiia. 2008, 48, 58–68.
- Obrezan, A.G.; Kulikov, N.V. Chronic Heart Failure and Diabetes Mellitus: Pathogenesis and Possibilities of Treatment. Kardiologiia 2018, 58, 85–94. [Google Scholar] [CrossRef]
- Aaron, Y. Kluger; Kristen, M. Tecson; Andy, Y. Lee; Edgar, V. Lerma; Janani Rangaswami; Norman, E. Lepor; Michael, E. Cobble; Peter, A. McCullough. Class effects of SGLT2 inhibitors on cardiorenal outcomes. Cardiovasc Diabetol. 2019, 18, 99. [Google Scholar] [CrossRef]
- Simeon, B. Simeonov; Nikolay, P. Botushanov; Dimitar, A. Iliev; Haralambus, K. Husianitis. Amaryl (glimepiride) in patients with type 2 diabetes mellitus. Folia Med. (Plovdiv). 2002, 44, 15–19. [Google Scholar]
- Comaschi, M.; Corsi, A.; Di Pietro, C.; Bellatreccia, A.; Mariz, S. COM06 Study Investigators. The effect of pioglitazone as add-on therapy to metformin or sulphonylurea compared to a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia. Nutr. Metab. Cardiovasc. Dis. 2008, 18, 373–379. [Google Scholar] [CrossRef]
- Copyright© 2025 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.
- Davies, L.E.; Spiers, G.; Kingston, A.; Todd, A.; Adamson, J.; Hanratty, B. Adverse Outcomes of Polypharmacy in Older People: Systematic Review of Reviews. J. Am. Med. Dir. Assoc. 2020, 21, 181–187. [Google Scholar] [CrossRef]
- Hilmer, S.N. ADME-tox issues for the elderly. Expert. Opin. Drug Metab. Toxicol. 2008, 4, 1321–1331. [Google Scholar] [CrossRef]
- Mitchell, S.J.; Hilmer, S.N. Drug-induced liver injury in older adults. Ther. Adv. Drug Saf. 2010, 1, 65–77. [Google Scholar] [CrossRef]
- Sarro, A.; Esposito, R.; Zibetti, A.; Pecere, A. Acute pancreatitis caused by methimazole/carbimazole assumption: A case-series. Minerva Endocrinol. (Torino). 2023, 48, 115–120. [Google Scholar] [CrossRef]
Figure 1.
Prevalence of diabetes mellitus in worldwide.
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