Orally Bioavailable Antagonists of Inhibitor of Apoptosis Proteins Based on an Azabicyclooctane Scaffold
Journal of Medicinal Chemistry2009Vol. 52(6), pp. 1723–1730
Citations Over TimeTop 10% of 2009 papers
Frederick Cohen, Bruno Alicke, Linda O. Elliott, John A. Flygare, Tatiana Goncharov, Stephen F. Keteltas, Matthew C. Franklin, Stacy M. Frankovitz, Jean-Philippe Stéphan, Vickie Tsui, Domagoj Vucic, Harvey Wong, Wayne J. Fairbrother
Abstract
A series of IAP antagonists based on an azabicyclooctane scaffold was designed and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values of 140, 38, and 33 nM, respectively. These compounds promote degradation of c-IAP1, activate caspases, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model.
Related Papers
- → Effect of retinol on iron bioavailability from Iranian bread in a Caco-2 cell culture model(2006)20 cited
- → Dissolution Systems for Chloramphenicol Tablet Bioavailability(1979)15 cited
- → Bioavailability of cyclandelate from capsules in beagle dogs and dissolution rate: Correlations with bioavailability in humans.(1991)5 cited
- → Study of the bioavailability of different formulations of 8‐methoxypsoralen in the dog(1988)4 cited
- → Prediction of Bioavailability(2003)2 cited