4kzc | pdb_00004kzc

Structure of PI3K gamma with Imidazopyridine inhibitors

spinqualitylabelsall models 4kzc, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kzc 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: 1UK, SO4 Related: 4kz0 Gene: PIK3CG (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed PI3 kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. The PI3 Kinase pathway is often de-regulated in cancer through PI3Kalpha overexpression, gene amplification, mutations and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe how the potency of a benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping. This effort led to the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties. Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K.,Pecchi S, Ni ZJ, Han W, Smith A, Lan J, Burger M, Merritt H, Wiesmann M, Chan J, Kaufman S, Knapp MS, Janssen J, Huh K, Voliva CF Bioorg Med Chem Lett. 2013 Jun 12. pii: S0960-894X(13)00719-1. doi:, 10.1016/j.bmcl.2013.06.010. PMID:23820386 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

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