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Literature summary extracted from

  • Fales, K.R.; Njoroge, F.G.; Brooks, H.B.; Thibodeaux, S.; Torrado, A.; Si, C.; Toth, J.L.; Mc Cowan, J.R.; Roth, K.D.; Thrasher, K.J.; Frimpong, K.; Lee, M.R.; Dally, R.D.; Shepherd, T.A.; Durham, T.B.; Margolis, B.J.; Wu, Z.; Wang, Y.; Atwell, S.; Wang, J.; Hui, Y.H.; Meier, T.I.; Konicek, S.A.; Geeganage, S.
    Discovery of N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a potent and selective nonclassical antifolate aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT) inhibitor (2017), J. Med. Chem., 60, 9599-9616 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.1.2.3 expressed in Escherichia coli BL21(DE3) cells Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.2.3 3-[(4-cyanobenzene-1-sulfonyl)amino]benzamide
-
 Homo sapiens
2.1.2.3 4-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl)benzene-1-sulfonamide
-
 Homo sapiens
2.1.2.3 4-cyano-N-(1-oxo-1,2-dihydroisoquinolin-7-yl)benzene-1-sulfonamide
-
 Homo sapiens
2.1.2.3 4-cyano-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)benzene-1-sulfonamide
-
 Homo sapiens
2.1.2.3 4-cyano-N-phenylbenzene-1-sulfonamide
-
 Homo sapiens
2.1.2.3 5-(5,5-dimethyl-6-oxo-1,4-dihydropyridin-3-yl)-N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 5-(5-ethyl-5-methyl-6-oxo-1,4-dihydropyridin-3-yl)-N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 5-[(3R,4S)-3-fluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 5-[(3S,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 5-[(4R)-3,3-difluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 5-[(4S)-3,3-difluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 methotrexate
-
 Homo sapiens
2.1.2.3 N-(2-amino-4-oxo-3,4-dihydroquinazolin-6-yl)-4-cyanobenzene-1-sulfonamide
-
 Homo sapiens
2.1.2.3 N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-(4-hydroxypiperidin-1-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide LSN 3213128, potent and selective inhibitor Homo sapiens
2.1.2.3 N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-(6-oxo-1H-pyridin-3-yl)thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-[(3R)-3-hydroxy-1-piperidyl]thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-[(3S)-3-hydroxy-1-piperidyl]thiophene-2-sulfonamide
-
 Homo sapiens
2.1.2.3 N-[(4-[[(2-amino-4-oxo-3,4-dihydroquinazolin-6-yl)amino]sulfonyl]-phenyl)carbonyl]-L-glutamic acid
-
 Homo sapiens
2.1.2.3 pemetrexed
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.2.3 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide Homo sapiens
-
 tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.2.3 Homo sapiens P31939
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.1.2.3 Ni-NTA agarose resin column chromatography and Superdex 200 gel filtration Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.1.2.3 MDA-MB-231-Met2 cell
-
 Homo sapiens
-
2.1.2.3 NCI-H460 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.2.3 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
-
 Homo sapiens tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.1.2.3 AICARFT
-
 Homo sapiens
2.1.2.3 aminoimidazole-4-carboxamide ribonucleotide formyltransferase
-
 Homo sapiens
2.1.2.3 ATIC bifunctional enzyme showing 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and inosine monophosphate cyclohydrolase activities Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.1.2.3 0.000005
-
 IC50 below 0.000005 mM, at pH 7.5 and 25°C Homo sapiens 5-(5,5-dimethyl-6-oxo-1,4-dihydropyridin-3-yl)-N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000005
-
 IC50 below 0.000005 mM, at pH 7.5 and 25°C Homo sapiens 5-(5-ethyl-5-methyl-6-oxo-1,4-dihydropyridin-3-yl)-N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000005
-
 IC50 below 0.000005 mM, at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-(6-oxo-1H-pyridin-3-yl)thiophene-2-sulfonamide
2.1.2.3 0.0000078
-
 at pH 7.5 and 25°C Homo sapiens 5-[(3S,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000012
-
 at pH 7.5 and 25°C Homo sapiens 5-[(4R)-3,3-difluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000013
-
 at pH 7.5 and 25°C Homo sapiens 5-[(4S)-3,3-difluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000013
-
 at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-(4-hydroxypiperidin-1-yl)thiophene-2-sulfonamide
2.1.2.3 0.000014
-
 at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide
2.1.2.3 0.000016
-
 at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide
2.1.2.3 0.000018
-
 at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-[(3S)-3-hydroxy-1-piperidyl]thiophene-2-sulfonamide
2.1.2.3 0.00002
-
 at pH 7.5 and 25°C Homo sapiens 5-[(3R,4S)-3-fluoro-4-hydroxypyrrolidin-1-yl]-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)thiophene-2-sulfonamide
2.1.2.3 0.000026
-
 at pH 7.5 and 25°C Homo sapiens N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)-5-[(3R)-3-hydroxy-1-piperidyl]thiophene-2-sulfonamide
2.1.2.3 0.000608
-
 at pH 7.5 and 25°C Homo sapiens 4-cyano-N-(1-oxo-1,2-dihydroisoquinolin-7-yl)benzene-1-sulfonamide
2.1.2.3 0.000723
-
 at pH 7.5 and 25°C Homo sapiens 4-cyano-N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)benzene-1-sulfonamide
2.1.2.3 0.0181
-
 at pH 7.5 and 25°C Homo sapiens N-(2-amino-4-oxo-3,4-dihydroquinazolin-6-yl)-4-cyanobenzene-1-sulfonamide
2.1.2.3 0.0348
-
 at pH 7.5 and 25°C Homo sapiens 4-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl)benzene-1-sulfonamide
2.1.2.3 0.09
-
 at pH 7.5 and 25°C Homo sapiens 3-[(4-cyanobenzene-1-sulfonyl)amino]benzamide
2.1.2.3 0.1
-
 IC50 above 0.1 mM, at pH 7.5 and 25°C Homo sapiens 4-cyano-N-phenylbenzene-1-sulfonamide