Literature summary for 2.7.11.25 extracted from

Tan, L.; Nomanbhoy, T.; Gurbani, D.; Patricelli, M.; Hunter, J.; Geng, J.; Herhaus, L.; Zhang, J.; Pauls, E.; Ham, Y.; Choi, H.G.; Xie, T.; Deng, X.; Buhrlage, S.J.; Sim, T.; Cohen, P.; Sapkota, G.; Westover, K.D.; Gray, N.S.
Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) (2015), J. Med. Chem., 58, 183-196.

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Activating Compound

Activating Compound	Comment	Organism	Structure
TGFbeta	TGFbeta-activated kinase 1	Homo sapiens

Crystallization (Commentary)

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

Inhibitors	Comment	Organism
(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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
A-375 cell	-	Homo sapiens	-
Huh-7 cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
MAP3K7	-	Homo sapiens
TAK1	-	Homo sapiens
TGFbeta-activated kinase 1	-	Homo sapiens