Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC3495162 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
Journal of medicinal chemistry 20121002 19
Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K(i) < 1 ...[more]