2xx8

Crystal structure of N,N-dimethyl-4-(3-(trifluoromethyl)-4,5,6,7- tetrahydro-1H-indazol-1-yl)benzamide in complex with the ligand binding domain of the Rat GluA2 receptor and glutamate at 2.2A resolution.

spinqualitylabelsall models 2xx8, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xx8 is a 3 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: 1NE, GLU, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A novel series of AMPAR positive modulators is described that were identified by high throughput screening. The molecules of the series have been optimized from a high quality starting point hit to afford excellent developability, tolerability, and efficacy profiles, leading to identification of a clinical candidate. Unusually for an ion channel target, this optimization was integrated with regular generation of ligand-bound crystal structures and uncovered a novel chemotype with a unique and highly conserved mode of interaction via a trifluoromethyl group. Integration of Lead Optimization with Crystallography for a Membrane-Bound Ion Channel Target: Discovery of a New Class of AMPA Receptor Positive Allosteric Modulators.,Ward SE, Harries M, Aldegheri L, Austin NE, Ballantine S, Ballini E, Bradley DM, Bax BD, Clarke BP, Harris AJ, Harrison SA, Melarange RA, Mookherjee C, Mosley J, Dal Negro G, Oliosi B, Smith KJ, Thewlis KM, Woollard PM, Yusaf SP J Med Chem. 2010 Dec 3. PMID:21128618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutamate receptor 3D structures

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