4j6i

Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase beta isoformDiscovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase beta isoform

Structural highlights 4j6i is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: p110 gamma, PIK3CG (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A series of suitable five-membered heterocyclic alternatives to thiophenes within a thienobenzoxepin class of PI3-kinase (PI3K) inhibitors was discovered. Specific thiazolobenzoxepin 8-substitution was identified that increased selectivity over PI3Kbeta. PI3Kbeta-sparing compound 27 (PI3Kbeta Ki,app/PI3Kalpha Ki,app=57) demonstrated dose-dependent knockdown of pAKT, pPRAS40 and pS6RP in vivo as well as differential effects in an in vitro proliferation cell line screen compared to pan PI3K inhibitor GDC-0941. A new structure-based hypothesis for reducing inhibition of the PI3K beta isoform while maintaining activity against alpha, delta and gamma isoforms is presented. Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase beta isoform.,Staben ST, Ndubaku C, Blaquiere N, Belvin M, Bull RJ, Dudley D, Edgar K, Gray D, Heald R, Heffron TP, Jones GE, Jones M, Kolesnikov A, Lee L, Lesnick J, Lewis C, Murray J, McLean NJ, Nonomiya J, Olivero AG, Ord R, Pang J, Price S, Prior WW, Rouge L, Salphati L, Sampath D, Wallin J, Wang L, Wei B, Weismann C, Wu P Bioorg Med Chem Lett. 2013 May 1;23(9):2606-13. doi: 10.1016/j.bmcl.2013.02.102. , Epub 2013 Mar 7. PMID:23540645 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

spinqualitylabelsall models 4j6i, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image