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Literature summary for 2.3.1.20 extracted from

  • Li, D.; Yin, J.; Li, J.; Nan, F.
    Design and synthesis of diacylglycerol acyltransferase 1 inhibitors based on Aphadilactone C (2016), Chinese J. Org. Chem., 36, 1359-1367 .
No PubMed abstract available
Search for more literature for 2.3.1.20

Application

Application Comment Organism
medicine diacylglycerol acyltransferase (DGAT), the only limited enzyme in the synthesis of triacylglycerol (TAG), is regarded as an important therapeutic target for human obesity and other metabolic syndromes Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(4S,7R)-4-(5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-2,2-dimethyl-4,7-bis[(4E)-4-methyl-5-[(2R)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]pent-4-en-1-yl]-4,5,6,7-tetrahydro-1-benzofuran-3(2H)-one 89.23% inhibition Homo sapiens
3,5-dimethyl-6-([(6E)-6-methyl-7-[(2S)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]hept-6-en-1-yl]oxy)pyrazine-2-carboxamide
-
 Homo sapiens
4-amino-6-[(4E)-4-methyl-5-[(2R)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]pent-4-en-2-yn-1-yl]-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one
-
 Homo sapiens
4-amino-6-[(4E)-4-methyl-5-[(2S)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]pent-4-en-2-yn-1-yl]-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one
-
 Homo sapiens
additional information design and synthesis of diacylglycerol acyltransferase 1 inhibitors based on aphadilactone C. The lactone group of aphadilactone C is introduced into the [(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl]acetic acid and [(1r,4r)-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid (which have entered into clinical research) to verify whether the lactone in aphadilactone C plays the same role as carboxylic group in [(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl]acetic acid and [(1r,4r)-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid. The final in vitro assay shows that the synthesized compounds have not the inhibition activity to DGAT1. This might suggest that the inhibition mechanism of aphadilactone C is not the same as of [(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl]acetic acid and [(1r,4r)-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid. No inhibition by 3,5-dimethyl-6-[(1E)-1-[(2S)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]prop-1-en-2-yl]pyrazine-2-carboxamide Homo sapiens
[(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl]acetic acid
-
 Homo sapiens
[(1r,4r)-4-[4-(5-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyridin-2-yl)phenyl]cyclohexyl]acetic acid
-
 Homo sapiens
[(1r,4r)-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid 89.32% inhibition Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acyl-CoA + 1,2-diacyl-sn-glycerol Homo sapiens
-
 CoA + 1,2,3-triacylglycerol
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O75907
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acyl-CoA + 1,2-diacyl-sn-glycerol
-
 Homo sapiens CoA + 1,2,3-triacylglycerol
-
 ?

Synonyms

Synonyms Comment Organism
DGAT1
-
 Homo sapiens
diacylglycerol acyltransferase 1
-
 Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000019
-
 pH 7.4, temperature not specified in the publication Homo sapiens [(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl]acetic acid
0.00008
-
 pH 7.4, temperature not specified in the publication Homo sapiens [(1r,4r)-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid
0.00046
-
 pH 7.4, temperature not specified in the publication Homo sapiens (4S,7R)-4-(5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)-2,2-dimethyl-4,7-bis[(4E)-4-methyl-5-[(2R)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]pent-4-en-1-yl]-4,5,6,7-tetrahydro-1-benzofuran-3(2H)-one