Empiriko
Advancing Outcomes Through Innovation

Conference: ACS Abstracts

Abstracts for Upcoming ACS Meeting in San Francisco (August 10 - 14, 2014)

Abstracts for Upcoming ACS Meeting in San Francisco (August 10 - 14, 2014)

Empiriko’s CSO Mukund Chorghade, Ph.D. presents at American Chemical Society National Meeting & Exposition, San Francisco, CA, August 10-14, 2014

Biomimiks™ as Chemosynthetic Livers: predict, prepare and prove the structure, activity and toxicity of drug metabolites

Abstract

We report advances in proprietary in vitro green chemistry-based Biomimiks™ technology, mimicking in vivo metabolism of several chemical entities used in pharmaceuticals, cosmetics, and agrochemicals. Biomimiks™ enables prediction of metabolism patterns and introduces new paradigms for drug discovery and drug-drug interactions for clinical diagnostics.

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.

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 scientists to conduct more complete in vitro metabolism studies, confirm structure and generate quantitative measures of toxicity. Biomimiks™ is an animal-free platform that identifies a more complete set of safety-relevant drug metabolites while keeping up with the rapid pace of drug development.

Chemosynthetic Livers: evaluating plausible drug-drug interactions relating to metabolite suppression or attenuation with Biomimiks™

Abstract

Polypharmacy, involving co-administration of several drugs, is common among the elderly and chronically ill. It is a risk factor for adverse drug reactions (ADRs) and drug-drug interactions (DDIs). One plausible DDI occurs when a drug interferes with another, causing irreversible changes to formation of metabolites from one or both. Such suppression or accentuation of metabolism could cause variances in toxicity and/or efficacy. We report experiments to predict and confirm modulation of oxidative metabolites from several combinations of common drugs for cancer, diabetes, hypercholesterolemia and hypertension in the presence of each other. Recent papers indicate best evidence for the dimerization of some compounds in diluted aqueous solution or assorted complex formation between disparate compounds.

Biomimiks™ technology (in vitro and ex vivo) is designed to mimic the in vivo oxidative metabolism mediated by cytochromes P450. This can be applied at the individual patient level for chemistry-based diagnostics to determine comparative effectiveness and safety.