Document Report Card

ID: ALA2086363

Journal: ACS Med Chem Lett

Title: Lipophilic Isosteres of a π-π Stacking Interaction: New Inhibitors of the Bcl-2-Bak Protein-Protein Interaction.

Authors: Yusuff N, Doré M, Joud C, Visser M, Springer C, Xie X, Herlihy K, Porter D, Touré BB.

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.

CiteXplore: 24900514

DOI: 10.1021/ml300095a