Description
A-1210477 is an inhibitor of the antiapoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1; K
i = 0.43 nM and IC
50 = 26.2 nM) that demonstrates >100-fold selectivity over other Bcl-2 family members (K
is > 0.66 μM for Bcl-2, Bcl-XL, Bcl-W, and Bfl-1). It has been shown to disrupt the interaction between Mcl-1 and pro-apoptotic BIM, inducing the hallmarks of apoptosis in Mcl-1-dependent multiple myeloma and non-small cell lung cancer cell lines.
References
[1]. lopez j, bessou m, riley js, et al. mito-priming as a method to engineer bcl-2 addiction. nature communications, 2016, 7:10538.
[2]. besbes s, mirshahi m, pocard m, et al. new dimension in therapeutic targeting of bcl-2 family proteins. oncotarget, 2015, 6(15): 12862.
[3]. leverson jd, zhang h, chen j, et al. potent and selective small-molecule mcl-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with abt-263 (navitoclax). cell death & disease, 2015, 6(1): e1590.
[4]. mott jl, kobayashi s, bronk sf, et al. mir-29 regulates mcl-1 protein expression and apoptosis. oncogene, 2007, 26(42): 6133-6140.
[5]. opferman jt. attacking cancer's achilles heel: antagonism of anti-apoptotic bcl-2 family members. febs journal, 2015.
