Lipophilic Isosteres of a pi-pi Stacking Interaction: Design of New Inhibitors of the Bcl-2-Bak Protein-Protein Interaction.
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 |
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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 |