| Structural highlights
Publication Abstract from PubMed
Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kbeta/delta dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kbeta and delta isoforms in the treatment of a number of inflammatory diseases.
Discovery and in Vivo Evaluation of Dual PI3Kbeta/delta Inhibitors.,Gonzalez-Lopez de Turiso F, Shin Y, Brown M, Cardozo M, Chen Y, Fong D, Hao X, He X, Henne K, Hu YL, Johnson MG, Kohn T, Lohman J, McBride HJ, McGee LR, Medina JC, Metz D, Miner K, Mohn D, Pattaropong V, Seganish J, Simard JL, Wannberg S, Whittington DA, Yu G, Cushing TD J Med Chem. 2012 Sep 13;55(17):7667-85. Epub 2012 Aug 29. PMID:22876881[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gonzalez-Lopez de Turiso F, Shin Y, Brown M, Cardozo M, Chen Y, Fong D, Hao X, He X, Henne K, Hu YL, Johnson MG, Kohn T, Lohman J, McBride HJ, McGee LR, Medina JC, Metz D, Miner K, Mohn D, Pattaropong V, Seganish J, Simard JL, Wannberg S, Whittington DA, Yu G, Cushing TD. Discovery and in Vivo Evaluation of Dual PI3Kbeta/delta Inhibitors. J Med Chem. 2012 Sep 13;55(17):7667-85. Epub 2012 Aug 29. PMID:22876881 doi:http://dx.doi.org/10.1021/jm300679u
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