3otq | pdb_00003otq
Soluble Epoxide Hydrolase in complex with pyrazole antagonist
Structural highlights
Function[HYES_HUMAN] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.[1] [2] Publication Abstract from PubMedA novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles. Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain.,Lo HY, Man CC, Fleck RW, Farrow NA, Ingraham RH, Kukulka A, Proudfoot JR, Betageri R, Kirrane T, Patel U, Sharma R, Hoermann MA, Kabcenell A, Lombaert SD Bioorg Med Chem Lett. 2010 Nov 15;20(22):6379-83. Epub 2010 Sep 19. PMID:20934334[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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