5K0I

mpges1 bound to an inhibitor

Summary for 5K0I

• Entry DOI: 10.2210/pdb5k0i/pdb
• Descriptor: Prostaglandin E synthase, 1,5-anhydro-2,3,4-trideoxy-3-{[(4S)-3,3-dimethyl-1-(8-methylquinolin-2-yl)piperidine-4-carbonyl]amino}-D-erythro-hexitol, GLUTATHIONE, ... (6 entities in total)
• Functional Keywords: mpges1, inhibitor, pain, inflammation, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19015.61

Authors

Luz, J.G.,Kuklish, S.L. (deposition date: 2016-05-17, release date: 2016-09-14, Last modification date: 2025-04-02)

Primary citation

Kuklish, S.L.,Antonysamy, S.,Bhattachar, S.N.,Chandrasekhar, S.,Fisher, M.J.,Fretland, A.J.,Gooding, K.,Harvey, A.,Hughes, N.E.,Luz, J.G.,Manninen, P.R.,McGee, J.E.,Navarro, A.,Norman, B.H.,Partridge, K.M.,Quimby, S.J.,Schiffler, M.A.,Sloan, A.V.,Warshawsky, A.M.,York, J.S.,Yu, X.P.
Characterization of 3,3-dimethyl substituted N-aryl piperidines as potent microsomal prostaglandin E synthase-1 inhibitors.
Bioorg.Med.Chem.Lett., 26:4824-4828, 2016

PubMed Abstract: 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 30μM, and failed to inhibit human mPGES-2 at 62.5μM 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.

PubMed: 27554445
DOI: 10.1016/j.bmcl.2016.08.023

Experimental method

X-RAY DIFFRACTION (1.3 Å)