5k0i
From Proteopedia
mpges1 bound to an inhibitor
Structural highlights
Function[PTGES_HUMAN] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).[1] Publication Abstract from PubMedHere 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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