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target has curated data in GtoImmuPdb
Target id: 2082
Nomenclature: mitogen-activated protein kinase kinase kinase 7
Abbreviated Name: TAK1
Family: TAK1 subfamily
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 606 | 6q15 | MAP3K7 | mitogen-activated protein kinase kinase kinase 7 | |
Mouse | - | 579 | 4 A5 | Map3k7 | mitogen-activated protein kinase kinase kinase 7 | |
Rat | - | 606 | 5q21 | Map3k7 | mitogen activated protein kinase kinase kinase 7 |
Previous and Unofficial Names |
Map3k7 | TAK1 | TGF-beta activated kinase 1 | transforming growth factor beta-activated kinase 1 |
Database Links | |
Alphafold | O43318 (Hs), Q62073 (Mm), P0C8E4 (Rn) |
BRENDA | 2.7.11.25 |
ChEMBL Target | CHEMBL5776 (Hs) |
Ensembl Gene | ENSG00000135341 (Hs), ENSMUSG00000028284 (Mm), ENSRNOG00000005724 (Rn) |
Entrez Gene | 6885 (Hs), 26409 (Mm), 313121 (Rn) |
Human Protein Atlas | ENSG00000135341 (Hs) |
KEGG Enzyme | 2.7.11.25 |
KEGG Gene | hsa:6885 (Hs), mmu:26409 (Mm), rno:313121 (Rn) |
OMIM | 602614 (Hs) |
Pharos | O43318 (Hs) |
RefSeq Nucleotide | NM_003188 (Hs), NM_172688 (Mm), NM_001107920 (Rn) |
RefSeq Protein | NP_003179 (Hs), NP_766276 (Mm), NP_001101390 (Rn) |
SynPHARM |
81146 (in complex with 5Z-7-oxozeaenol) 84134 (in complex with compound 12 [PMID: 27448772]) 81137 (in complex with NG-25) 84542 (in complex with Takinib) |
UniProtKB | O43318 (Hs), Q62073 (Mm), P0C8E4 (Rn) |
Wikipedia | MAP3K7 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
5Z-7-oxozeaenol inhibits the ATPase activity of a TAK1/TAB1 fusion protein with an IC50 of 14nM [18]. |
DiscoveRx KINOMEscan® screen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 6,17 |
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Target used in screen: TAK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,7 |
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Target used in screen: TAK1/TAK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [5,11]. This enzyme is the subject of drug discovery programmes for inflammatory disorders, as well as for cancer [10-11]. Scarneo et al. (2018) have validated TAK1 inhibition as a therapeutic strategy that can effectively inhibit macrophage TNF secretion using genetic and pharmacological techniques [12]. |
Immuno Process Associations | ||
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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Barf T, Kaptein A. (2012) Irreversible protein kinase inhibitors: balancing the benefits and risks. J Med Chem, 55 (14): 6243-62. [PMID:22621397]
3. Brown K, Vial SC, Dedi N, Long JM, Dunster NJ, Cheetham GM. (2005) Structural basis for the interaction of TAK1 kinase with its activating protein TAB1. J Mol Biol, 354 (5): 1013-20. [PMID:16289117]
4. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]
5. Dai L, Aye Thu C, Liu XY, Xi J, Cheung PC. (2012) TAK1, more than just innate immunity. IUBMB Life, 64 (10): 825-34. [PMID:22941947]
6. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
7. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
8. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J Med Chem, 55 (2): 903-13. [PMID:22148921]
9. McIver EG, Bryans J, Birchall K, Chugh J, Drake T, Lewis SJ, Osborne J, Smiljanic-Hurley E, Tsang W, Kamal A et al.. (2012) Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases. Bioorg Med Chem Lett, 22 (23): 7169-73. [PMID:23099093]
10. Muraoka T, Ide M, Morikami K, Irie M, Nakamura M, Miura T, Kamikawa T, Nishihara M, Kashiwagi H. (2016) Discovery of a potent and highly selective transforming growth factor β receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD). Bioorg Med Chem, 24 (18): 4206-17. [PMID:27448772]
11. Sakurai H. (2012) Targeting of TAK1 in inflammatory disorders and cancer. Trends Pharmacol Sci, 33 (10): 522-30. [PMID:22795313]
12. Scarneo SA, Mansourati A, Eibschutz LS, Totzke J, Roques JR, Loiselle D, Carlson D, Hughes P, Haystead TAJ. (2018) Genetic and pharmacological validation of TAK1 inhibition in macrophages as a therapeutic strategy to effectively inhibit TNF secretion. Sci Rep, 8 (1): 17058. [PMID:30451876]
13. Sogabe Y, Matsumoto T, Hashimoto T, Kirii Y, Sawa M, Kinoshita T. (2015) 5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner. Bioorg Med Chem Lett, 25 (3): 593-6. [PMID:25529738]
14. Tan L, Gurbani D, Weisberg EL, Jones DS, Rao S, Singer WD, Bernard FM, Mowafy S, Jenney A, Du G et al.. (2017) Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. Bioorg Med Chem, 25 (4): 1320-1328. [PMID:28038940]
15. Tan L, Nomanbhoy T, Gurbani D, Patricelli M, Hunter J, Geng J, Herhaus L, Zhang J, Pauls E, Ham Y et al.. (2015) Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2). J Med Chem, 58 (1): 183-96. [PMID:25075558]
16. Totzke J, Gurbani D, Raphemot R, Hughes PF, Bodoor K, Carlson DA, Loiselle DR, Bera AK, Eibschutz LS, Perkins MM et al.. (2017) Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease. Cell Chem Biol, 24 (8): 1029-1039.e7. [PMID:28820959]
17. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
18. Wu J, Powell F, Larsen NA, Lai Z, Byth KF, Read J, Gu RF, Roth M, Toader D, Saeh JC et al.. (2013) Mechanism and In Vitro Pharmacology of TAK1 Inhibition by (5Z)-7-Oxozeaenol. ACS Chem Biol, 8 (3): 643-50. [PMID:23272696]
TAK1 subfamily: mitogen-activated protein kinase kinase kinase 7. Last modified on 26/11/2018. Accessed on 07/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2082.