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Literature summary for 1.1.1.146 extracted from

  • Wu, S.C.; Yoon, D.; Chin, J.; van Kirk, K.; Seethala, R.; Golla, R.; He, B.; Harrity, T.; Kunselman, L.K.; Morgan, N.N.; Ponticiello, R.P.; Taylor, J.R.; Zebo, R.; Harper, T.W.; Li, W.; Wang, M.; Zhang, L.; Sleczka, B.G.; Nayeem, A.; Sheriff, S.; Camac, D.M.; Morin, P.E.; Everlof, J.G.; Li, Y.X.; Ferraro, C.A.; et al.
    Discovery of 3-hydroxy-4-cyano-isoquinolines as novel, potent, and selective inhibitors of human 11beta-hydroxydehydrogenase 1 (11beta-HSD1) (2011), Bioorg. Med. Chem. Lett., 21, 6693-6698.
    View publication on PubMed
Search for more literature for 1.1.1.146

Cloned(Commentary)

Cloned (Comment) Organism
expression in HEK-293 cell Homo sapiens
expression in HEK-293 cell Mus musculus

Crystallization (Commentary)

Crystallization (Comment) Organism
co-crystal structure of inhibitor 8-[[(2-cyanopyridin-3-yl)methyl]sulfanyl]-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile with enzyme and cofactor NADP+. Structure shows a critical H-bonding interaction between the OH pharmacophore of the inhibitor and the side chains of S170 and Y183 residues at the catalytic site of the enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1-[(2-chlorobenzyl)oxy]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile compound with a superior metabolic stability profile, but sub-optimal with respect to aqueous solubility Homo sapiens
1-[(2-chlorobenzyl)oxy]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile compound with a superior metabolic stability profile, but sub-optimal with respect to aqueous solubility Mus musculus
1-[(2-chlorobenzyl)sulfanyl]-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile good inhibitory activity. Compound undergoes oxidative metabolism at several sites Homo sapiens
1-[(2-chlorobenzyl)sulfanyl]-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile good inhibitory activity. Compound undergoes oxidative metabolism at several sites Mus musculus
1-[(2-chlorobenzyl)sulfanyl]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile overall good inhibitory activity and metabolic stability Homo sapiens
1-[(2-chlorobenzyl)sulfanyl]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile overall good inhibitory activity and metabolic stability Mus musculus
2-[(2-chlorobenzyl)sulfanyl]-4-hydroxy-6-phenylpyrimidine-5-carbonitrile lead compound for development of inhibitors, the hydroxypyrimidine may act as a H-bonding pharmacophore. Compound has good cross species 11beta-HSD1 inhibitory activity for the mouse, cynomolgus monkey, and human enzymes Homo sapiens
2-[(2-chlorobenzyl)sulfanyl]-4-hydroxy-6-phenylpyrimidine-5-carbonitrile lead compound for development of inhibitors, the hydroxypyrimidine may act as a H-bonding pharmacophore. Compound has good cross species 11beta-HSD1 inhibitory activity for the mouse, cynomolgus monkey, and human enzymes Mus musculus
8-[[(2-cyanopyridin-3-yl)methyl]sulfanyl]-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile
-
 Homo sapiens
8-[[(2-cyanopyridin-3-yl)methyl]sulfanyl]-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile
-
 Mus musculus

Organism

Organism UniProt Comment Textmining
Homo sapiens P28845
-
-
Mus musculus P50172
-
-

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000002
-
 22°C, pH not specified in the publication, assay on microsomes Homo sapiens 1-[(2-chlorobenzyl)sulfanyl]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile
0.000005
-
 22°C, pH not specified in the publication, assay on microsomes Homo sapiens 1-[(2-chlorobenzyl)sulfanyl]-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
0.000005
-
 22°C, pH not specified in the publication, assay on microsomes Mus musculus 1-[(2-chlorobenzyl)sulfanyl]-3-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
0.000007
-
 22°C, pH not specified in the publication, assay on microsomes Mus musculus 1-[(2-chlorobenzyl)sulfanyl]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile
0.000008
-
 22°C, pH not specified in the publication, assay on microsomes Homo sapiens 1-[(2-chlorobenzyl)oxy]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile
0.000012
-
 22°C, pH not specified in the publication, assay on microsomes Homo sapiens 8-[[(2-cyanopyridin-3-yl)methyl]sulfanyl]-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile
0.000021
-
 22°C, pH not specified in the publication, assay on microsomes Mus musculus 1-[(2-chlorobenzyl)oxy]-7-fluoro-3-hydroxyisoquinoline-4-carbonitrile
0.000027
-
 22°C, pH not specified in the publication, assay on microsomes Homo sapiens 2-[(2-chlorobenzyl)sulfanyl]-4-hydroxy-6-phenylpyrimidine-5-carbonitrile
0.000058
-
 22°C, pH not specified in the publication, assay on microsomes Mus musculus 2-[(2-chlorobenzyl)sulfanyl]-4-hydroxy-6-phenylpyrimidine-5-carbonitrile
0.000105
-
 22°C, pH not specified in the publication, assay on microsomes Mus musculus 8-[[(2-cyanopyridin-3-yl)methyl]sulfanyl]-6-hydroxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine-5-carbonitrile