Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.
 

Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.

Related Articles Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.

Bioorg Med Chem Lett. 2010 Sep 15;

Authors: Petros AM, Huth JR, Oost T, Park CM, Ding H, Wang X, Zhang H, Nimmer P, Mendoza R, Sun C, Mack J, Walter K, Dorwin S, Gramling E, Ladror U, Rosenberg SH, Elmore SW, Fesik SW, Hajduk PJ

The Bcl-2 family of proteins plays a major role in the regulation of apoptosis, or programmed cell death. Overexpression of the anti-apoptotic members of this family (Bcl-2, Bcl-x(L), and Mcl-1) can render cancer cells resistant to chemotherapeutic agents and therefore these proteins are important targets for the development of new anti-cancer agents. Here we describe the discovery of a potent, highly selective, Bcl-2 inhibitor using SAR by NMR and structure-based drug design which could serve as a starting point for the development of a Bcl-2 selective anti-cancer agent. Such an agent would potentially overcome the Bcl-x(L) mediated thrombocytopenia observed with ABT-263.

PMID: 20870405 [PubMed - as supplied by publisher]



Source: PubMed