Publication Abstract from PubMed
Phosphoinositide 3-kinase gamma (PI3Kgamma) is an attractive target to potentially treat a range of disease states. Herein, we describe the evolution of a reported phenylthiazole pan-PI3K inhibitor into a family of potent and selective benzothiazole inhibitors. Using X-ray crystallography, we discovered that compound 22 occupies a previously unreported hydrophobic binding cleft adjacent to the ATP binding site of PI3Kgamma, and achieves its selectivity by exploiting natural sequence differences among PI3K isoforms in this region.
Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma,Collier PN, Martinez-Botella G, Cornebise M, Cottrell KM, Doran JD, Griffith JP, Mahajan S, Maltais F, Moody CS, Huck EP, Wang T, Aronov AM J Med Chem. 2014 May 2. PMID:24754609[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
