Literature summary for 3.1.1.13 extracted from

Dato, F.M.; Sheikh, M.; Uhl, R.Z.; Schueller, A.W.; Steinkrueger, M.; Koch, P.; Neudoerfl, J.M.; Guetschow, M.; Goldfuss, B.; Pietsch, M.
omega-Phthalimidoalkyl aryl ureas as potent and selective inhibitors of cholesterol esterase (2018), ChemMedChem, 13, 1833-1847 .

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of C-terminally double-StrepII-tagged enzyme in HEK-293 EBNA cells	Homo sapiens
recombinant expression of C-terminally double-StrepII-tagged enzyme in HEK-293 EBNA cells	Mus musculus

Inhibitors

Inhibitors	Comment	Organism
2-(dimethylamino)-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one	noncompetitive inhibition	Homo sapiens
2-(dimethylamino)-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one	-	Mus musculus
2-(dimethylamino)-6,7-dihydro-4H,5H-cyclopenta[4,5]thieno[2,3-d][1,3]oxazin-4-one	noncompetitive inhibition	Homo sapiens
2-(dimethylamino)-6,7-dihydro-4H,5H-cyclopenta[4,5]thieno[2,3-d][1,3]oxazin-4-one	-	Mus musculus
4-[3,5-bis(trifluoromethyl)phenyl]-N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]piperazine-1-carboxamide	65.2% activity compared to control, at 0.025 mM	Homo sapiens
4-[3,5-bis(trifluoromethyl)phenyl]-N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]piperazine-1-carboxamide	95.3% activity compared to control, at 0.025 mM	Mus musculus
additional information	omega-phthalimidoalkyl aryl ureas as potent and selective inhibitors of cholesterol esterase, synthesis and inhibitory potencies. The urea motif with an attached 3,5-bis(trifluoromethyl)phenyl group and the aromatic character of the omega-phthalimide residue are most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, is an optimal spacer for inhibitors. Structure-activity relationships depending on the spacer length and urea/amide motif, overview	Homo sapiens
additional information	omega-phthalimidoalkyl aryl ureas as potent and selective inhibitors of cholesterol esterase, synthesis and inhibitory potencies. The urea motif with an attached 3,5-bis(trifluoromethyl)phenyl group and the aromatic character of the omega-phthalimide residue are most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, is an optimal spacer for inhibitors, Structure-activity relationships depending on the spacer length and urea/amide motif, overview	Mus musculus
N-(3,5-dichlorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	104% activity compared to control, at 0.025 mM	Homo sapiens
N-(3,5-dichlorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	100% activity compared to control, at 0.025 mM	Mus musculus
N-(3,5-difluorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	103% activity compared to control, at 0.025 mM	Homo sapiens
N-(3,5-difluorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	88.4% activity compared to control, at 0.025 mM	Mus musculus
N-(3,5-dimethoxyphenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	110% activity compared to control, at 0.025 mM	Homo sapiens
N-(3,5-dimethoxyphenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	103% activity compared to control, at 0.025 mM	Mus musculus
N-(3,5-dimethylphenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	105% activity compared to control, at 0.025 mM	Homo sapiens
N-(3,5-dimethylphenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	94.7% activity compared to control, at 0.025 mM	Mus musculus
N-(3,5-dinitrophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	80.5% activity compared to control, at 0.025 mM	Homo sapiens
N-(3,5-dinitrophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	85.3% activity compared to control, at 0.025 mM	Mus musculus
N-(4-bromophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	104% activity compared to control, at 0.025 mM	Homo sapiens
N-(4-bromophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	94.5% activity compared to control, at 0.025 mM	Mus musculus
N-(4-chlorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	112% activity compared to control, at 0.025 mM	Homo sapiens
N-(4-chlorophenyl)-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	64.0% activity compared to control, at 0.025 mM	Mus musculus
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-2-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	72.5% activity compared to control, at 0.025 mM	Homo sapiens
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-2-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	87.8% activity compared to control, at 0.025 mM	Mus musculus
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-3-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	100% activity compared to control, at 0.025 mM	Homo sapiens
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-3-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	73.5% activity compared to control, at 0.025 mM	Mus musculus
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-4-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	90.2% activity compared to control, at 0.025 mM	Homo sapiens
N-[3',5'-bis(trifluoromethyl)[1,1'-biphenyl]-4-yl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	58.2% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanamide	81.3% activity compared to control, at 0.025 mM; 91.1% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanamide	71.8% activity compared to control, at 0.025 mM; 90.8% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]urea	97.4% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]urea	108% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3,4,5,6,7-hexahydro-2H-isoindol-2-yl)propyl]urea	64.8% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3,4,5,6,7-hexahydro-2H-isoindol-2-yl)propyl]urea	71.0% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	noncompetitive inhibition, 64.1% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	5.25% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,4S,7R,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl]propyl]urea	84.8% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,4S,7R,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl]propyl]urea	96.6% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-isoindol-2-yl]propyl]urea	72.4% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,7aS)-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-isoindol-2-yl]propyl]urea	82.9% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,7aS)-1,3-dioxooctahydro-2H-isoindol-2-yl]propyl]urea	80.6% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-[(3aR,7aS)-1,3-dioxooctahydro-2H-isoindol-2-yl]propyl]urea	89.1% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]urea	competitive inhibition, 68.5% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]urea	15.6% activity compared to control, at 0.025 mM	Mus musculus
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentyl]urea	49.3% activity compared to control, at 0.025 mM	Homo sapiens
N-[3,5-bis(trifluoromethyl)phenyl]-N'-[5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentyl]urea	22.5% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-4-phenylpiperazine-1-carboxamide	106% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-4-phenylpiperazine-1-carboxamide	101% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-fluorophenyl)urea	107% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-fluorophenyl)urea	101% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-methoxyphenyl)urea	107% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-methoxyphenyl)urea	90.4% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-methylphenyl)urea	105% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-methylphenyl)urea	100% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-nitrophenyl)urea	85.3% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-(4-nitrophenyl)urea	76.5% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-phenylurea	108% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-phenylurea	107% activity compared to control, at 0.025 mM	Mus musculus
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-[4-(trifluoromethyl)phenyl]urea	116% activity compared to control, at 0.025 mM	Homo sapiens
N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]-N'-[4-(trifluoromethyl)phenyl]urea	92.5% activity compared to control, at 0.025 mM	Mus musculus

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P19835	-	-
Mus musculus	Q64285	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant C-terminally double-StrepII-tagged enzyme from HEK-293 EBNA cells by affinity chromatography	Homo sapiens
recombinant C-terminally double-StrepII-tagged enzyme from HEK-293 EBNA cells by affinity chromatography	Mus musculus

Source Tissue

Source Tissue	Comment	Organism	Textmining
commercial preparation	-	Homo sapiens	-
commercial preparation	-	Mus musculus	-
pancreas	-	Homo sapiens	-
pancreas	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
4-methylumbelliferyl butyrate + H2O	-	Homo sapiens	4-methylumbelliferol + butyrate	-	?
4-methylumbelliferyl butyrate + H2O	-	Mus musculus	4-methylumbelliferol + butyrate	-	?

Synonyms

Synonyms	Comment	Organism
BAL	-	Homo sapiens
BAL	-	Mus musculus
bile-salt activated lipase	-	Homo sapiens
bile-salt activated lipase	-	Mus musculus
cel	-	Homo sapiens
cel	-	Mus musculus
cholesterol esterase	-	Homo sapiens
cholesterol esterase	-	Mus musculus
hCEase	-	Homo sapiens
mCEase	-	Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
30	-	assay at	Homo sapiens
30	-	assay at	Mus musculus

pH Optimum

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

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.0000341	-	2-(dimethylamino)-6,7-dihydro-4H,5H-cyclopenta[4,5]thieno[2,3-d][1,3]oxazin-4-one	pH 7.0, 30°C, recombinant enzyme	Mus musculus
0.000262	-	2-(dimethylamino)-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one	pH 7.0, 30°C, recombinant enzyme	Mus musculus
0.00119	-	N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	pH 7.0, 30°C, recombinant enzyme	Mus musculus
0.00431	-	2-(dimethylamino)-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one	pH 7.0, 30°C, recombinant enzyme	Homo sapiens
0.00434	-	2-(dimethylamino)-6,7-dihydro-4H,5H-cyclopenta[4,5]thieno[2,3-d][1,3]oxazin-4-one	pH 7.0, 30°C, recombinant enzyme	Homo sapiens
0.01	-	N-[3,5-bis(trifluoromethyl)phenyl]-N'-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]urea	pH 7.0, 30°C, recombinant enzyme	Homo sapiens
0.0118	-	N-[3,5-bis(trifluoromethyl)phenyl]-N'-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]urea	pH 7.0, 30°C, recombinant enzyme	Homo sapiens
0.0187	-	N-[3,5-bis(trifluoromethyl)phenyl]-N'-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butyl]urea	pH 7.0, 30°C, recombinant enzyme	Mus musculus