| Structural highlights
Publication Abstract from PubMed
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model.
Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of PI3-kinase.,Staben ST, Heffron TP, Sutherlin DP, Bhat SR, Castanedo GM, Chuckowree IS, Dotson J, Folkes AJ, Friedman LS, Lee L, Lesnick J, Lewis C, Murray JM, Nonomiya J, Olivero AG, Plise E, Pang J, Prior WW, Salphati L, Rouge L, Sampath D, Tsui V, Wan NC, Wang S, Weismann C, Wu P, Zhu BY Bioorg Med Chem Lett. 2010 Oct 15;20(20):6048-51. Epub 2010 Aug 19. PMID:20822905[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Staben ST, Heffron TP, Sutherlin DP, Bhat SR, Castanedo GM, Chuckowree IS, Dotson J, Folkes AJ, Friedman LS, Lee L, Lesnick J, Lewis C, Murray JM, Nonomiya J, Olivero AG, Plise E, Pang J, Prior WW, Salphati L, Rouge L, Sampath D, Tsui V, Wan NC, Wang S, Weismann C, Wu P, Zhu BY. Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of PI3-kinase. Bioorg Med Chem Lett. 2010 Oct 15;20(20):6048-51. Epub 2010 Aug 19. PMID:20822905 doi:10.1016/j.bmcl.2010.08.067
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