Timpani, C.A.; Rasmussen, L.; Rybalka, E. Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo. Pharmaceuticals2023, 16, 1458.
Timpani, C.A.; Rasmussen, L.; Rybalka, E. Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo. Pharmaceuticals 2023, 16, 1458.
Timpani, C.A.; Rasmussen, L.; Rybalka, E. Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo. Pharmaceuticals2023, 16, 1458.
Timpani, C.A.; Rasmussen, L.; Rybalka, E. Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo. Pharmaceuticals 2023, 16, 1458.
Abstract
Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.
Keywords
adenylosuccinic acid; Duchenne muscular dystrophy; myopathy; metabolic disease; skeletal muscle; toxicology; drug development
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
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