Literature summary for 3.3.2.10 extracted from

Amano, Y.; Tanabe, E.; Yamaguchi, T.
Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening (2015), Bioorg. Med. Chem., 23, 2310-2317 .

Application

Application	Comment	Organism
drug development	soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene EPHX2, recombinant expression of C-terminally His6-tagged full-length enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme as apo-crystals of sEH by sitting drop vapor diffusion method, mixing of 15-20 mg/ml protein with reservoir solution containing 0.1 M potassium phosphate, pH 7.5, 0.2 M ammonium dihydrogen phosphate, and 22% w/v PEG 3350, 3-4 days, for inhibitor complexed crystals, soaking in 10 mM ligand in mother liquor for 4 h at room temperature, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement method using PDB ID 1S8O as a search model	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme as apo-crystals of sEH by sitting drop vapor diffusion method, mixing of 15-20 mg/ml protein with reservoir solution containing 0.1 M potassium phosphate, pH 7.5, 0.2 M ammonium dihydrogen phosphate, and 22% w/v PEG 3350, 3-4 days, for inhibitor complexed crystals, soaking in 10 mM ligand in mother liquor for 4 h at room temperature, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement method using PDB ID 1S8O as a search model

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(1S,3R)-N-[[4-cyano-2-(trifluoromethyl)phenyl]methyl]-3-[[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino]cyclohexane-1-carboxamide	GSK2256294	Homo sapiens
(4-bromo-3-cyclopropyl-1H-pyrazol-1-yl)acetic acid	-	Homo sapiens
1-[3-(trifluoromethyl)pyridin-2-yl]piperazine	-	Homo sapiens
1-[4-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-ol	-	Homo sapiens
2-(2-fluorophenyl)-N-[(5-methylthiophen-2-yl)methyl]ethan-1-amine	-	Homo sapiens
2-(piperazin-1-yl)pyridine-3-carbonitrile	-	Homo sapiens
2-([[2-(adamantan-1-yl)ethyl]amino]methyl)phenol	-	Homo sapiens
3-[4-(benzyloxy)phenyl]propan-1-ol	-	Homo sapiens
additional information	identification of N-ethylmethylamine as a scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening, overview. N-Ethylmethylamine is identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold are selected from a chemical library and evaluated for inhibitory potency. Enzyme-inhibitor interaction analysis	Homo sapiens
N,N'-dicyclohexylurea	DCU	Homo sapiens
N-(1-acetylpiperidin-4-yl)-N'-adamantan-1-ylurea	-	Homo sapiens
N-(1-tert-butoxyethenyl)-1,2,3,4-tetrahydroquinolin-3-amine	-	Homo sapiens
N-methyl-1-[3-(pyridin-3-yl)phenyl]methanamine	-	Homo sapiens
N-[(1-methyl-1H-pyrazol-3-yl)methyl]-2-phenylethan-1-amine	-	Homo sapiens
trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid	t-AUCB	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P34913	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant C-terminally His6-tagged full-length enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, followed by gel filtration	Homo sapiens

Synonyms

Synonyms	Comment	Organism
SEH	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at room temperature	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	-	assay at	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.00051	-	37°C, pH 7.0	Homo sapiens	2-([[2-(adamantan-1-yl)ethyl]amino]methyl)phenol
0.009	-	37°C, pH 7.0	Homo sapiens	2-(2-fluorophenyl)-N-[(5-methylthiophen-2-yl)methyl]ethan-1-amine
0.052	-	37°C, pH 7.0	Homo sapiens	1-[4-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-ol
0.091	-	37°C, pH 7.0	Homo sapiens	(4-bromo-3-cyclopropyl-1H-pyrazol-1-yl)acetic acid
0.15	-	37°C, pH 7.0	Homo sapiens	3-[4-(benzyloxy)phenyl]propan-1-ol
0.58	-	37°C, pH 7.0	Homo sapiens	N-(1-tert-butoxyethenyl)-1,2,3,4-tetrahydroquinolin-3-amine
0.8	-	37°C, pH 7.0	Homo sapiens	N-[(1-methyl-1H-pyrazol-3-yl)methyl]-2-phenylethan-1-amine
1.2	-	37°C, pH 7.0	Homo sapiens	1-[3-(trifluoromethyl)pyridin-2-yl]piperazine
2.2	-	37°C, pH 7.0	Homo sapiens	N-methyl-1-[3-(pyridin-3-yl)phenyl]methanamine