Journal of Medicinal Chemistry 2008-04-24

Identification of promiscuous small molecule activators in high-throughput enzyme activation screens.

David R Goode, Ryan K Totten, James T Heeres, Paul J Hergenrother

Index: J. Med. Chem. 51 , 2346-9, (2008)

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Abstract

It is recognized that high-throughput enzyme inhibition screens often return nonspecific inhibitors as "hits". Recently, high-throughput screens for enzyme activators have led to the identification of several compounds with novel and potent biological activity. Here, we show that enzyme activation screens can also uncover compounds that activate multiple enzymes in a nonspecific fashion. Described herein are the general structural features of such compounds and methods to differentiate between specific and general enzyme activation.