1. Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)
- Author
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Patricia A. Elkins, Steven R. Skinner, G Joseph Franklin, Nicholas D. Adams, Joelle Lorraine Burgess, Michael D. Schaber, Kenneth E Lind, Kaushik Raha, Ghotas Evindar, Yun Ding, Hongfang Yang, Paolo A. Centrella, Ruth Lehr, Steven D. Knight, Jennifer L. DeLorey, Kurt R. Auger, Sibongile Mataruse, John W. Cuozzo, Patricia F Medeiros, Schmidt Stanley J, and Matthew A. Clark
- Subjects
Gene isoform ,Chemotype ,Organic Chemistry ,Mutant ,Wild type ,Computational biology ,Biology ,P110α ,Biochemistry ,Small molecule ,Molecular biology ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,DNA - Abstract
In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.
- Published
- 2015
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