Version 1
: Received: 28 August 2023 / Approved: 28 August 2023 / Online: 29 August 2023 (03:25:53 CEST)
How to cite:
Benardout, M.; Le Gresley, A.; El Shaer, A.; Wren, S.P. Application of fSP3 towards Non-Systemic Drug Discovery. Preprints2023, 2023081882. https://doi.org/10.20944/preprints202308.1882.v1
Benardout, M.; Le Gresley, A.; El Shaer, A.; Wren, S.P. Application of fSP3 towards Non-Systemic Drug Discovery. Preprints 2023, 2023081882. https://doi.org/10.20944/preprints202308.1882.v1
Benardout, M.; Le Gresley, A.; El Shaer, A.; Wren, S.P. Application of fSP3 towards Non-Systemic Drug Discovery. Preprints2023, 2023081882. https://doi.org/10.20944/preprints202308.1882.v1
APA Style
Benardout, M., Le Gresley, A., El Shaer, A., & Wren, S.P. (2023). Application of fSP3 towards Non-Systemic Drug Discovery. Preprints. https://doi.org/10.20944/preprints202308.1882.v1
Chicago/Turabian Style
Benardout, M., Amr El Shaer and Stephen P. Wren. 2023 "Application of fSP3 towards Non-Systemic Drug Discovery" Preprints. https://doi.org/10.20944/preprints202308.1882.v1
Abstract
Non-systemic oral drugs, which do not get absorbed through the gastrointestinal membrane, are an important group of compounds for targeting diseases residing within the gastrointestinal lumen. However, they require a set of design principles not sufficiently covered by traditional druglikeness metrics, such as Lipinski’s Rule of 5. These druglikeness metrics fail to accurately identify true negative outcomes; such is the requirement for novel cheminformatic based approaches for the discovery of non-systemic small molecules. One such example of these newer metrics is the fraction of SP3-hybridised carbon atoms (fSP3) which has shown promising application as an identifier of poor oral-bioavailability. Herein, we discuss the application of fSP3 in the drug discovery process in a number of case studies, including our own work discovering non-systemic fructose scavengers for the treatment of fructose malabsorption.
Keywords
fSP3; drug design; bioavailability; non-systemic drugs; druglikeness; cheminformatics
Subject
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
