Application | Comment | Organism |
---|---|---|
drug development | aminoquinazoline pyridones are potent, selective, and orally efficacious c-Kit inhibitors for the treatment of fibrotic diseases. Compounds show greater than 200fold selectivity against KDR, p38, Lck, and Src | Mus musculus |
drug development | aminoquinazoline pyridones are potent, selective, and orally efficacious c-Kit inhibitors for the treatment of fibrotic diseases. Compounds show greater than 200fold selectivity against KDR, p38, Lck, and Src | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
co-crystallization of pyridone, bisamide or 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one with the V916T mutant KDR protein | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
V916T | KDR mutant, which shares the majority of residues with c-Kit in the ATP binding pocket. Inhibitor 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one binds in the DFG-out conformation. Two nitrogens from the aminoquinazoline portion of the molecule form hydrogen bonding interactions with linker region of the enzyme at Cys673. The pyridone scaffold is further anchored by the hydrogen bond contacts between its carbonyl group and Asp810 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one | cyclopentylethyl | Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one | pyridone, nonselective inhibitor of c-Kit | Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one | exhibits poor selectivity | Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one | - |
Mus musculus | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one | exhibits potent inhibition of c-Kit, greater than 200fold selectivity against KDR, p38, Lck, and Src, and desirable pharmacokinetic properties | Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one | - |
Homo sapiens | |
3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one | - |
Homo sapiens | |
ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate | - |
Homo sapiens | |
imatinib | - |
Homo sapiens | |
N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide | bisamide | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P35968 | - |
- |
Mus musculus | P05532 | C57BL/6 mice | - |
Mus musculus C57BL/6 | P05532 | C57BL/6 mice | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
mast cell | - |
Mus musculus | - |
UT-7 cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
c-kit | - |
Mus musculus |
KDR | - |
Homo sapiens |
receptor tyrosine kinase c-Kit | - |
Mus musculus |
receptor tyrosine kinase c-Kit | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000001 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one | |
0.0000021 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one | |
0.0000061 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.0000079 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one | |
0.00001 | - |
c-Kit | Homo sapiens | 1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.000011 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-tert-butylphenyl)-4-methylpyridin-2(1H)-one | |
0.000013 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one | |
0.000014 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one | |
0.000014 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one | |
0.000017 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one | |
0.000017 | - |
c-Kit | Homo sapiens | ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate | |
0.00002 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one | |
0.00002 | - |
c-Kit | Homo sapiens | 1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.000022 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one | |
0.00004 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one | |
0.000048 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3,3-dimethylindolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.000052 | - |
c-Kit | Homo sapiens | imatinib | |
0.00006 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one | |
0.000065 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one | |
0.000077 | - |
c-Kit | Homo sapiens | N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide | |
0.00021 | - |
c-Kit | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one | |
0.001 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-phenylpyridin-2(1H)-one | |
0.0014 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2(1H)-one | |
0.0018 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one | |
0.0034 | - |
KDR | Homo sapiens | 1-(4-(1H-pyrazol-1-yl)phenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.0043 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-fluoro-3-methylphenyl)-4-methylpyridin-2(1H)-one | |
0.0044 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-morpholinophenyl)pyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-methoxyphenyl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-chlorophenyl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3-methoxyphenyl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(4-chloro-3-fluorophenyl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-1-(3-fluoro-4-methylphenyl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | 1-(4-acetylphenyl)-3-(2-aminoquinazolin-6-yl)-4-methylpyridin-2(1H)-one | |
0.005 | - |
KDR | Homo sapiens | ethyl 4-(3-(2-aminoquinazolin-6-yl)-4-methyl-2-oxopyridin-1(2H)-yl)benzoate | |
0.005 | - |
KDR | Homo sapiens | 3-(2-aminoquinazolin-6-yl)-4-methyl-1-(4-(oxazol-2-yl)phenyl)pyridin-2(1H)-one | |
0.025 | - |
KDR | Homo sapiens | imatinib | |
0.025 | - |
KDR | Homo sapiens | N3-(6-aminopyridin-3-yl)-N1-(2-cyclopentylethyl)-4-methylisophthalamide |