Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo.
Cara A TimpaniLorna RasmussenEmma RybalkaPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year clinical trial data on Duchenne muscular dystrophy patients suggests it is a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and its acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD 50 > 5000 mg/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.
Keyphrases
- small molecule
- duchenne muscular dystrophy
- protein protein
- clinical trial
- end stage renal disease
- electronic health record
- drug induced
- oxidative stress
- ejection fraction
- chronic kidney disease
- newly diagnosed
- big data
- liver failure
- prognostic factors
- peritoneal dialysis
- endothelial cells
- randomized controlled trial
- respiratory failure
- systematic review
- type diabetes
- open label
- intensive care unit
- emergency department
- high fat diet induced
- study protocol
- insulin resistance
- double blind
- extracorporeal membrane oxygenation