7pop

PI3 kinase delta in complex with 5-[3,6-dihydro-2H-pyran-4-yl]-2-methoxy-N-[2-methylpyridin-4-yl]pyridine-3-sulfonamide

spinqualitylabelsall models 7pop, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.491Å Ligands: 7VT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Optimization of a previously reported lead series of PI3Kdelta inhibitors with a novel binding mode led to the identification of a clinical candidate compound 31 (GSK251). Removal of an embedded Ames-positive heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9. Further optimization to avoid glutathione trapping, to enhance potency and selectivity, and to optimize an oral pharmacokinetic profile led to the discovery of compound 31 (GSK215) that had a low predicted daily dose (45 mg, b.i.d) and a rat toxicity profile suitable for further development. Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kdelta with a Novel Binding Mode.,Down K, Amour A, Anderson NA, Barton N, Campos S, Cannons EP, Clissold C, Convery MA, Coward JJ, Doyle K, Duempelfeld B, Edwards CD, Goldsmith MD, Krause J, Mallett DN, McGonagle GA, Patel VK, Rowedder J, Rowland P, Sharpe A, Sriskantharajah S, Thomas DA, Thomson DW, Uddin S, Hamblin JN, Hessel EM J Med Chem. 2021 Sep 23;64(18):13780-13792. doi: 10.1021/acs.jmedchem.1c01102., Epub 2021 Sep 11. PMID:34510892 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-kinase 3D structures

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