Literature summary for 3.3.2.10 extracted from

Eldrup, A.B.; Soleymanzadeh, F.; Taylor, S.J.; Muegge, I.; Farrow, N.A.; Joseph, D.; McKellop, K.; Man, C.C.; Kukulka, A.; De Lombaert, S.
Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase (2009), J. Med. Chem., 52, 5880-5895.

Application

Application	Comment	Organism
drug development	sEH is a target for drug design, since inhibition of sEH leads to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties	Homo sapiens
drug development	sEH is a target for drug design, since inhibition of sEH leads to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties	Rattus norvegicus

Cloned(Commentary)

Cloned (Comment)	Organism
expression of sEH using a baculovirus expression	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant apoenzyme in complex with inhibitors N-(3,3-diphenyl-propyl)-nicotinamide and 4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide, hanging drop vapour diffusion method, 0.005 ml of protein solution containing 12 mg/ml protein in 100 mM sodium phosphate pH 7.4, 50 mM NaCl and 3 mM DTT, is mixed with 0.005 ml of reservoir solution containing 0.2 M lithium sulfate, 36% PEG 3350, and 0.1 M Tris pH 8.4, and 500 nl of 0.006 mM beta-D-hexadecyl maltoside, 4°C, 1 week, X-ray diffraction structure determination and analysis at 1.95-2.5 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant apoenzyme in complex with inhibitors N-(3,3-diphenyl-propyl)-nicotinamide and 4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide, hanging drop vapour diffusion method, 0.005 ml of protein solution containing 12 mg/ml protein in 100 mM sodium phosphate pH 7.4, 50 mM NaCl and 3 mM DTT, is mixed with 0.005 ml of reservoir solution containing 0.2 M lithium sulfate, 36% PEG 3350, and 0.1 M Tris pH 8.4, and 500 nl of 0.006 mM beta-D-hexadecyl maltoside, 4°C, 1 week, X-ray diffraction structure determination and analysis at 1.95-2.5 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide	-	Homo sapiens
(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide	-	Rattus norvegicus
(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide	-	Homo sapiens
(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide	-	Rattus norvegicus
(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide	-	Homo sapiens
(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide	-	Rattus norvegicus
(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide	-	Homo sapiens
(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide	-	Rattus norvegicus
3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propylamine	-	Homo sapiens
3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propylamine	-	Rattus norvegicus
4,4-diphenyl-N-(pyridin-3-yl)-butyramide	-	Homo sapiens
4,4-diphenyl-N-(pyridin-3-yl)-butyramide	-	Rattus norvegicus
4-cyano-N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide	-	Homo sapiens
4-cyano-N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide	-	Rattus norvegicus
additional information	synthesis and structure-based optimization of arylamides sEH inhibitors based on the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide, overview. Assessment of inhibitor stability in liver microsomes, overview	Homo sapiens
additional information	synthesis and structure-based optimization of arylamides sEH inhibitors based on the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide, overview. Assessment of inhibitor stability in liver microsomes, overview	Rattus norvegicus
N-(2,2-diphenyl-ethyl)-nicotinamide	-	Homo sapiens
N-(2,2-diphenyl-ethyl)-nicotinamide	-	Rattus norvegicus
N-(3,3-diphenyl-propyl)-2-pyridine-3-ylacetamide	-	Homo sapiens
N-(3,3-diphenyl-propyl)-2-pyridine-3-ylacetamide	-	Rattus norvegicus
N-(3,3-diphenyl-propyl)-isonicotinamide	-	Homo sapiens
N-(3,3-diphenyl-propyl)-isonicotinamide	-	Rattus norvegicus
N-(3,3-diphenyl-propyl)-nicotinamide	-	Homo sapiens
N-(3,3-diphenyl-propyl)-nicotinamide	-	Rattus norvegicus
N-(3-phenyl-propyl)-nicotinamide	-	Homo sapiens
N-(3-phenyl-propyl)-nicotinamide	-	Rattus norvegicus
N-(4,4-diphenyl-butyl)-nicotinamide	-	Homo sapiens
N-(4,4-diphenyl-butyl)-nicotinamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-4-methanesulfonyl-benzamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-4-methanesulfonyl-benzamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-hydroxy-nicotinamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-hydroxy-nicotinamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide	-	Rattus norvegicus
N-[3,3-bis-(4-fluorophenyl)-propyl]-nicotinamide	-	Homo sapiens
N-[3,3-bis-(4-fluorophenyl)-propyl]-nicotinamide	-	Rattus norvegicus
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide	-	Homo sapiens
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide	-	Rattus norvegicus
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide	-	Homo sapiens
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide	-	Rattus norvegicus
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide	-	Homo sapiens
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide	-	Rattus norvegicus
pyridine-2-carboxylic acid (3,3-diphenyl-propyl)-amide	-	Homo sapiens
pyridine-2-carboxylic acid (3,3-diphenyl-propyl)-amide	-	Rattus norvegicus
pyridine-3-sulfonic acid 3,3-(diphenylpropyl)-amide	-	Homo sapiens
pyridine-3-sulfonic acid 3,3-(diphenylpropyl)-amide	-	Rattus norvegicus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
soluble	-	Homo sapiens	-	-
soluble	-	Rattus norvegicus	-	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O	Homo sapiens	-	(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid	-	?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O	Rattus norvegicus	-	(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O	Homo sapiens	-	(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O	Rattus norvegicus	-	(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O	Homo sapiens	-	(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O	Rattus norvegicus	-	(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid	-	?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O	Homo sapiens	-	(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid	-	?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O	Rattus norvegicus	-	(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P34913	-	-
Rattus norvegicus	P80299	male sprague-dawley rats	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
Hep-G2 cell	-	Homo sapiens	-
liver	-	Homo sapiens	-
liver	-	Rattus norvegicus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O	-	Homo sapiens	(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid	-	?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O	-	Rattus norvegicus	(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O	-	Homo sapiens	(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O	-	Rattus norvegicus	(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O	-	Homo sapiens	(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid	-	?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O	-	Rattus norvegicus	(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid	-	?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O	-	Homo sapiens	(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid	-	?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O	-	Rattus norvegicus	(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid	-	?

Synonyms

Synonyms	Comment	Organism
SEH	-	Homo sapiens
SEH	-	Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens
37	-	assay at	Rattus norvegicus

pH Optimum

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

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000004	-	-	Homo sapiens	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
0.0000048	-	-	Rattus norvegicus	N-(3,3-diphenyl-propyl)-nicotinamide
0.0000048	-	-	Rattus norvegicus	N-(3,3-diphenyl-propyl)-isonicotinamide
0.000005	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-6-hydroxy-nicotinamide
0.000005	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
0.000005	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide
0.000005	-	-	Homo sapiens	4-cyano-N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide
0.000005	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-4-methanesulfonyl-benzamide
0.0000051	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide
0.000006	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide
0.000006	-	-	Homo sapiens	(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
0.000006	-	-	Rattus norvegicus	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
0.000006	-	-	Rattus norvegicus	(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
0.000007	-	-	Homo sapiens	N-(3,3-diphenyl-propyl)-nicotinamide
0.000007	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-6-hydroxy-nicotinamide
0.000007	-	-	Rattus norvegicus	4-cyano-N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide
0.000007	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-4-methanesulfonyl-benzamide
0.000007	-	-	Rattus norvegicus	(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
0.000007	-	-	Homo sapiens	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide
0.000007	-	-	Rattus norvegicus	3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propylamine
0.0000072	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-nicotinamide
0.0000076	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-benzamide
0.0000079	-	-	Homo sapiens	N-(3,3-diphenyl-propyl)-isonicotinamide
0.000008	-	-	Homo sapiens	N-[3,3-bis-(4-fluorophenyl)-propyl]-nicotinamide
0.000008	-	-	Homo sapiens	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide
0.000008	-	-	Homo sapiens	(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
0.000008	-	-	Rattus norvegicus	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide
0.000009	-	-	Rattus norvegicus	N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
0.000014	-	-	Rattus norvegicus	N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide
0.000014	-	-	Homo sapiens	(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
0.000018	-	-	Rattus norvegicus	4,4-diphenyl-N-(pyridin-3-yl)-butyramide
0.000023	-	-	Homo sapiens	(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
0.000024	-	-	Rattus norvegicus	(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
0.000026	-	-	Rattus norvegicus	N-(4,4-diphenyl-butyl)-nicotinamide
0.000031	-	-	Homo sapiens	N-(3,3-diphenyl-propyl)-2-pyridine-3-ylacetamide
0.000045	-	-	Homo sapiens	4,4-diphenyl-N-(pyridin-3-yl)-butyramide
0.00007	-	-	Rattus norvegicus	N-(3-phenyl-propyl)-nicotinamide
0.000087	-	-	Rattus norvegicus	(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
0.0001	-	-	Homo sapiens	pyridine-2-carboxylic acid (3,3-diphenyl-propyl)-amide
0.00012	-	-	Homo sapiens	N-(4,4-diphenyl-butyl)-nicotinamide
0.00015	-	-	Rattus norvegicus	N-(3,3-diphenyl-propyl)-2-pyridine-3-ylacetamide
0.00043	-	-	Rattus norvegicus	pyridine-2-carboxylic acid (3,3-diphenyl-propyl)-amide
0.0007	-	-	Homo sapiens	N-(3-phenyl-propyl)-nicotinamide
0.003	-	-	Homo sapiens	N-(2,2-diphenyl-ethyl)-nicotinamide
0.003	-	-	Rattus norvegicus	N-(2,2-diphenyl-ethyl)-nicotinamide
0.003	-	-	Homo sapiens	pyridine-3-sulfonic acid 3,3-(diphenylpropyl)-amide
0.003	-	-	Rattus norvegicus	pyridine-3-sulfonic acid 3,3-(diphenylpropyl)-amide