5k0i

mpges1 bound to an inhibitor

spinqualitylabelsall models 5k0i, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k0i 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. Method: X-ray diffraction, Resolution 1.3Å Ligands: 6PW, BOG, CSO, GSH, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTGES_HUMAN Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Publication Abstract from PubMed Here we report on novel, potent 3,3-dimethyl substituted N-aryl piperidine inhibitors of microsomal prostaglandin E synthases-1(mPGES-1). Example 14 potently inhibited PGE2 synthesis in an ex vivo human whole blood (HWB) assay with an IC50 of 7nM. In addition, 14 had no activity in human COX-1 or COX-2 assays at 30muM, and failed to inhibit human mPGES-2 at 62.5muM in a microsomal prep assay. These data are consistent with selective mPGES-1-mediated reduction of PGE2. In dog, 14 had oral bioavailability (74%), clearance (3.62mL/(min*kg)) and volume of distribution (Vd,ss=1.6L/kg) values within our target ranges. For these reasons, 14 was selected for further study. Characterization of 3,3-dimethyl substituted N-aryl piperidines as potent microsomal prostaglandin E synthase-1 inhibitors.,Kuklish SL, Antonysamy S, Bhattachar SN, Chandrasekhar S, Fisher MJ, Fretland AJ, Gooding K, Harvey A, Hughes NE, Luz JG, Manninen PR, McGee JE, Navarro A, Norman BH, Partridge KM, Quimby SJ, Schiffler MA, Sloan AV, Warshawsky AM, York JS, Yu XP Bioorg Med Chem Lett. 2016 Oct 1;26(19):4824-8. doi: 10.1016/j.bmcl.2016.08.023. , Epub 2016 Aug 10. PMID:27554445 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prostaglandin E synthase

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