Cyclic marinopyrrole derivatives as disruptors of Mcl-1 and Bcl-x(L) binding to Bim

环状马里诺吡咯衍生物作为 Mcl-1 和 Bcl-x(L) 与 Bim 结合的干扰物

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作者:Chunwei Cheng, Yan Liu, Maria E Balasis, Nicholas L Simmons, Jerry Li, Hao Song, Lili Pan, Yong Qin, K C Nicolaou, Said M Sebti, Rongshi Li1

Abstract

A series of novel cyclic marinopyrroles were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-x(L), was evaluated using ELISA assays. Both atropisomers of marinopyrrole A (1) show similar potency. A tetrabromo congener 9 is two-fold more potent than 1. Two novel cyclic marinopyrroles (3 and 4) are two- to seven-fold more potent than 1.

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