3lj3 | pdb_00003lj3

PI3-kinase-gamma with a pyrrolopyridine-benzofuran inhibitor

spinqualitylabelsall models 3lj3, resolution 2.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lj3 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: SO4, WYE Gene: PIK3CG (Homo sapiens) Activity: Phosphatidylinositol-4,5-bisphosphate 3-kinase, with EC number 2.7.1.153 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed We discovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran- 3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3Kalpha. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3Kgamma revealed the key hydrogen bonding interactions. Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran- 3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR).,Tsou HR, MacEwan G, Birnberg G, Grosu G, Bursavich MG, Bard J, Brooijmans N, Toral-Barza L, Hollander I, Mansour TS, Ayral-Kaloustian S, Yu K Bioorg Med Chem Lett. 2010 Apr 1;20(7):2321-5. Epub 2010 Feb 2. PMID:20188552 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

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