Structural Insights into the Design of Small Molecule Inhibitors That Selectively Antagonize Mcl-1
Paul H. Bernardo, Thirunavukkarasu Sivaraman, Kah-Fei Wan, Jin Yi Xu, Janarthanan Krishnamoorthy, Chun Meng Song, Liming Tian, Jasmine S. F. Chin, Diane S. W. Lim, Henry Y. K. Mok, Victor Chun Kong Yu, Joo Chuan Tong, Christina L. L. Chai · Journal of Medicinal Chemistry · 2010
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 a possible rationale for the observed specificity.