Yusuff, Naeem, Dore, Michael, Joud, Carol, Visser, Michael, Springer, Clayton, Xie, Xiaoling, Herlihy, Kara, Porter, Dale and Toure, Bakary-Barry (2012) Lipophilic Isosteres of a pi-pi Stacking Interaction: Design of New Inhibitors of the Bcl-2-Bak Protein-Protein Interaction. ACS medicinal chemistry letters, 3 (7). pp. 579-583. ISSN 1948-5875

Abstract

The discovery of new Bcl-2 protein-protein interaction antagonists is described. We replaced the northern fragment of ABT737 (π- π stacking interactions) with structurally simplified hydrophobic cage structures with much reduced conformational flexibility and rotational freedom. The binding mode of the compounds was elucidated by x-ray crystallography, and the compounds showed excellent oral bioavailability and clearance in rat PK studies.

Item Type:	Article
Keywords:	Bcl-2 inhibitors, protein-protein interaction, π- π stacking interactions, π- π stacking isosteres, bioisoteres, cancer therapeutics.
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/6701