Wang Z1, Xu W1, Song T2, Guo Z2, Liu L1, Fan Y2, Wang A1, Zhang Z1.
Arch Pharm (Weinheim). 2016 Dec 2. doi: 10.1002/ardp.201600251. [Epub ahead of print]Based on a known selective Mcl-1 inhibitor, 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylic acid, we applied a fragment-based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl-1 over the Bcl-2 protein. After we deconstructed the 1H-indole-2-carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1-position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X-ray crystallography. Read More