4jnc

Soluble Epoxide Hydrolase complexed with a carboxamide inhibitor

spinqualitylabelsall models 4jnc, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jnc 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 1.96Å Ligands: 1LF Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed 1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure. Based on this lead optimization work, 1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-{[[4-bromo-2-(trifluoromethoxy) ]-phenyl]methyl}-4-piperidinecarboxamide (27) was identified as a useful tool compound for in vivo investigation. Robust effects on a serum biomarker, 9, 10-epoxyoctadec-12(Z)-enoic acid (the epoxide derived from linoleic acid) were observed, which provided evidence of robust in vivo target engagement and the suitability of 27 as a tool compound for study in various disease models. Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase.,Thalji RK, McAtee JJ, Belyanskaya S, Brandt M, Brown GD, Costell MH, Ding Y, Dodson JW, Eisennagel SH, Fries RE, Gross JW, Harpel MR, Holt DA, Israel DI, Jolivette LJ, Krosky D, Li H, Lu Q, Mandichak T, Roethke T, Schnackenberg CG, Schwartz B, Shewchuk LM, Xie W, Behm DJ, Douglas SA, Shaw AL, Marino JP Jr Bioorg Med Chem Lett. 2013 Jun 15;23(12):3584-8. doi: 10.1016/j.bmcl.2013.04.019., Epub 2013 Apr 16. PMID:23664879 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epoxide hydrolase 3D structures

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