| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1362753 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
Abstract
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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Steven T. Staben, Timothy P. Heffron, Daniel P. Sutherlin, Seema R. Bhat, Georgette M. Castanedo, Irina S. Chuckowree, Jenna Dotson, Adrian J. Folkes, Lori S. Friedman, Leslie Lee, John Lesnick, Cristina Lewis, Jeremy M. Murray, Jim Nonomiya,