your speakers for our 2 events

Biography

Konstantine Skordos is a Section Manager in Drug Metabolism and Pharmacokinetics at GSK.  He has been with GSK since 2003 after obtaining his Ph.D. and postdoctoral training at the University of Utah, both with Dr. Gary Yost.  His areas of research interest include drug bioactivation and its relevance to toxicity, biotransformation mechanisms, CYP inactivation, and in vitro-in vivo correlation for the prediction of drug interactions.  He currently leads a group of scientists engaged in in vitro mechanistic, drug metabolism studies.

Abstract

Reducing late stage attrition: Predicting hepatotoxicity in the clinic from early preclinical screening data

Hepatotoxicity is a leading cause of failed drug approvals and drug withdrawals, and of compound attrition both clinically and preclinically. During lead optimisation, assays are available, from both DMPK and Safety Assessment, to assess the potential of a compound to undergo metabolic activation and / or result in hepatotoxicity, but how predictive are these assays of hepatotoxicity in the clinic? This presentation details an extensive piece of analysis using 100’s of compounds with known hepatotoxicity status in the clinic, to interrogate the predictivity of these early screening assays. The results of this analysis have been used to develop a screening strategy that may help reduce late stage attrition due to hepatotoxicity.