Goode David R, Totten Ryan K, Heeres James T, Hergenrother Paul J
Department of Chemistry, Roger Adams Laboratory, University of Illinois, 600 S. Mathews Avenue, Urbana, Illinois 61801, USA.
J Med Chem. 2008 Apr 24;51(8):2346-9. doi: 10.1021/jm701583b. Epub 2008 Mar 27.
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.
人们认识到，高通量酶抑制筛选常常会将非特异性抑制剂作为“命中物”返回。最近，针对酶激活剂的高通量筛选已导致鉴定出几种具有新颖且强效生物活性的化合物。在此，我们表明酶激活筛选也能发现以非特异性方式激活多种酶的化合物。本文描述了此类化合物的一般结构特征以及区分特异性和一般性酶激活的方法。
