HTRF Resource Library

All roads to successful drug discovery lead through cell-based assays (and why shouldn' t they?)

By:  Dr Ralph J. Garippa

Roche, Inc Nutley, NJ USA 07110

Abstract
There are a number of daunting challenges to be faced in modern day drug development. These include intense competition from amongst domestic and foreign pharmaceutical and biotechnology interests with respect to intellectual property, “orphan” drug targets with sparsely-associated literature annotation, and a high public and FDA demand for novel specific drugs with high efficacy and low toxicity profiles. Increasingly, cell-based assay have consistently provided value-adding information to a number of core aspects in the quest for new medicinals by  (1) enabling cellular phenotypical characterization of inhibitory RNA knockdown of candidate proteins from all classes of drug targets (2) allowing the investigation of these targets in the correct cellular context, with pathway interactions and signaling responses intact (3) discriminating between desirable on-target and undesirable off-target functional effects, especially in cases where the latter can obscure the former (4) providing metrics for measuring the new physiological steady state which is established in the face of prolonged drug exposure (5) supporting early de-risking strategies using cellular estimates of genotoxicity and cytotoxicity as surrogates for eventual and inevitable in vivo data.