Details

Autor(en) / Beteiligte

• Yusuff, Naeem
• Doré, Michaël
• Joud, Carol
• Visser, Michael
• Springer, Clayton
• Xie, Xiaoling
• Herlihy, Kara
• Porter, Dale
• Touré, B. Barry

Titel

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

Ist Teil von

• ACS medicinal chemistry letters, 2012-07, Vol.3 (7), p.579-583

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.