3KOO

Crystal Structure of soluble epoxide Hydrolase

Summary for 3KOO

• Entry DOI: 10.2210/pdb3koo/pdb
• Descriptor: Epoxide hydrolase 2, N-(2,4-dichlorobenzyl)-4-(pyrimidin-2-yloxy)piperidine-1-carboxamide (3 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P34913
• Total number of polymer chains: 1
• Total formula weight: 63066.87

Authors

Farrow, N.A. (deposition date: 2009-11-13, release date: 2010-04-28, Last modification date: 2024-02-21)

Primary citation

Eldrup, A.B.,Soleymanzadeh, F.,Farrow, N.A.,Kukulka, A.,De Lombaert, S.
Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.
Bioorg.Med.Chem.Lett., 20:571-575, 2010

PubMed Abstract: Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.

PubMed: 19969453
DOI: 10.1016/j.bmcl.2009.11.091

Experimental method

X-RAY DIFFRACTION (2.791 Å)