Structural Insights into the Design of Small Molecule Inhibitors That Selectively Antagonize Mcl-1

The screening of a small focused library of rhodanine derivatives as inhibitors of Bcl-2 proteins led to the discovery of two structurally related compounds with different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent NMR studies with Mutant proteins and in silico docking studies provide it possible rationale for the observed specificity.