4ykn
Pi3K alpha lipid kinase with Active Site InhibitorPi3K alpha lipid kinase with Active Site Inhibitor
Structural highlights
Function[P85A_HUMAN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.[1] [2] [3] Publication Abstract from PubMedIn the search of PI3K p110alpha 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 p110alpha protein. Discovery of a Potent Class of PI3Kalpha Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).,Yang H, Medeiros PF, Raha K, Elkins P, Lind KE, Lehr R, Adams ND, Burgess JL, Schmidt SJ, Knight SD, Auger KR, Schaber MD, Franklin GJ, Ding Y, DeLorey JL, Centrella PA, Mataruse S, Skinner SR, Clark MA, Cuozzo JW, Evindar G ACS Med Chem Lett. 2015 Mar 20;6(5):531-6. doi: 10.1021/acsmedchemlett.5b00025., eCollection 2015 May 14. PMID:26005528[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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