2. Academic Validation
  3. 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

  • Bioorg Med Chem Lett. 2010 Nov 15;20(22):6587-91. doi: 10.1016/j.bmcl.2010.09.033.
Andrew M Petros 1,  Jeffrey R Huth,  Thorsten Oost,  Cheol-Min Park,  Hong Ding,  Xilu Wang,  Haichao Zhang,  Paul Nimmer,  Renaldo Mendoza,  Chaohong Sun,  Jamey Mack,  Karl Walter,  Sarah Dorwin,  Emily Gramling,  Uri Ladror,  Saul H Rosenberg,  Steven W Elmore,  Stephen W Fesik,  Philip J Hajduk
Affiliations

Affiliation

  • 1 Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, United States.
PMID: 20870405 DOI: 10.1016/j.bmcl.2010.09.033
Abstract

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.

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