Activating Compound | Comment | Organism | Structure |
---|---|---|---|
TGFbeta | TGFbeta-activated kinase 1 | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
10 mg/ml TAK1-TAB1 by hanging-drop method at 20°C, mixing of 0.004 ml of protein solution with 0004 ml of reservoir solution containing 0.65-0.75 M sodium citrate, 0.2 M NaCl, 0.1 M Tris, pH 7.0, and 5 mM adenosine, X-ray diffraction structure determination and analysis, molecular replacement with inactive TAK1-TAB1 structure, PDB cID 2YIY, as search model | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(E)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)-3-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)vinyl)-4-methylbenzamide | 88,5% inhibition of TAK1 at 500 nM | Homo sapiens | |
2-amino-1-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-2-[4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]ethanone | - |
Homo sapiens | |
3-((1H-pyrrolo[2,3-b]pyridin-4-yl)oxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide | a type II inhibitor, 97.1% inhibition of TAK1 at 500 nM | Homo sapiens | |
3-[(6,7-dimethoxyquinazolin-4-yl)oxy]-N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methylbenzamide | 83.7% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide | selectivity analysis with diverse enzymes, overview. 29.3% Inhibition of TAK1 at 0.001 mM | Homo sapiens | |
4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}-N-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]benzamide | selectivity analysis with diverse enzymes, overview. 7.0% Inhibition of TAK1 at 0.001 mM | Homo sapiens | |
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide | - |
Homo sapiens | |
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide | - |
Homo sapiens | |
4-methyl-N-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]-3-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)benzamide | 29.3% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
4-methyl-N-{4-[(1-methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)phenyl}-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide | - |
Homo sapiens | |
4-[(4-ethylpiperazin-1-yl)methyl]-N-{3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]phenyl}-3-(trifluoromethyl)benzamide | - |
Homo sapiens | |
4-[5-({4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}carbamoyl)-2-methylphenoxy]-N-methylpyridine-2-carboxamide | - |
Homo sapiens | |
BIRB796 | - |
Homo sapiens | |
imatinib | - |
Homo sapiens | |
additional information | discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1), a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines exhibit potent inhibitory activity against mitogen-activated protein kinase TAK1 (MAP3K7), overview. Identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. The activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. Inhibitor binding structure analysis, docking using the enzyme crystal structure, overview | Homo sapiens | |
N-[3-(2-cyanopropan-2-yl)phenyl]-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide | - |
Homo sapiens | |
N-[3-(2-cyanopropan-2-yl)phenyl]-4-methyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide | - |
Homo sapiens | |
N-[4-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide | - |
Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide | 75.6% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide | - |
Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide | - |
Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)benzamide | 77.7% inhibition of TAK1 at 0.001 mM; 86.5% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy)benzamide | 59.6% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-[(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]benzamide | 57.7% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide | 74.3% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-{[2-(methylamino)pyrimidin-4-yl]oxy}benzamide | 77.7% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}benzamide | 78.5% inhibition of TAK1 at 0.001 mM | Homo sapiens | |
N-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide | - |
Homo sapiens | |
nilotinib | - |
Homo sapiens | |
sorafenib | - |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
A-375 cell | - |
Homo sapiens | - |
Huh-7 cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
MAP3K7 | - |
Homo sapiens |
TAK1 | - |
Homo sapiens |
TGFbeta-activated kinase 1 | - |
Homo sapiens |