Chemosynthetic Livers: Predict, Prepare and Prove the Structure, Activity and Toxicity of Drug Metabolites
Mukund S. Chorghade
President and CSO
THINQ Pharmaceuticals, Inc.
UUÂãÁÄÖ±²¥Metabolites are implicated in adverse drug reactions and are the subject of intense scrutiny in drug R&D. Present-day processes involving animal studies are expensive, labor-intensive and chemically inconclusive. We report advances in proprietary in vitro green chemistry-based technology, mimicking in vivo metabolism of several chemical entities used in pharmaceuticals, cosmetics, and agrochemicals. Our catalysts enable prediction of metabolism patterns with soft-spot analysis and the methodology introduces new paradigms for drug discovery and drug-drug interactions for clinical diagnostics. Our catalysts (azamacrocycles) are sterically protected and electronically activated, providing speed, stability and scalability. We predict structures of metabolites, prepare them on a large scale by oxidation, and elucidate chemical structures. Comprehensive safety evaluation enables researchers to conduct more complete in vitro metabolism studies, confirm structure and generate quantitative measures of toxicity.
