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Target has curated data in GtoImmuPdb
Target id: 2040
Nomenclature: inhibitor of nuclear factor kappa B kinase subunit epsilon
Abbreviated Name: IKK-epsilon
Family: IKK family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 716 | 1q32.1 | IKBKE | inhibitor of nuclear factor kappa B kinase subunit epsilon | |
Mouse | - | 717 | 1 E4 | Ikbke | inhibitor of kappaB kinase epsilon | |
Rat | - | 717 | 13 q13 | Ikbke | inhibitor of nuclear factor kappa B kinase subunit epsilon |
Database Links | |
Alphafold | Q14164 (Hs), Q9R0T8 (Mm) |
BRENDA | 2.7.11.10 |
ChEMBL Target | CHEMBL3529 (Hs) |
Ensembl Gene | ENSG00000263528 (Hs), ENSMUSG00000042349 (Mm), ENSRNOG00000025100 (Rn) |
Entrez Gene | 9641 (Hs), 56489 (Mm), 363984 (Rn) |
Human Protein Atlas | ENSG00000263528 (Hs) |
KEGG Enzyme | 2.7.11.10 |
KEGG Gene | hsa:9641 (Hs), mmu:56489 (Mm), rno:363984 (Rn) |
OMIM | 605048 (Hs) |
Pharos | Q14164 (Hs) |
RefSeq Nucleotide | NM_001193321 (Hs), NM_019777 (Mm), NM_001108854 (Rn) |
RefSeq Protein | NP_054721 (Hs), NP_062751 (Mm), NP_001102324 (Rn) |
UniProtKB | Q14164 (Hs), Q9R0T8 (Mm) |
Wikipedia | IKBKE (Hs) |
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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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: 4,14 |
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Target used in screen: IKK-epsilon | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
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Target used in screen: nd/IKKe(IKBKE) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are constitutively and ubiquitously expressed. |
Immuno Process Associations | ||
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General Comments |
IKKε and TBK1 phosphorylate the transcription factors interferon (IFN) regulator factor (IRF) 3 and 7. This function is critical for the induction of the type I IFN response (induction of IFN genes and IFN-stimulated genes) in response to microbial infection [5,12]. |
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. Clark K, Peggie M, Plater L, Sorcek RJ, Young ER, Madwed JB, Hough J, McIver EG, Cohen P. (2011) Novel cross-talk within the IKK family controls innate immunity. Biochem J, 434 (1): 93-104. [PMID:21138416]
3. Clark K, Plater L, Peggie M, Cohen P. (2009) Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem, 284 (21): 14136-46. [PMID:19307177]
4. 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]
5. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T. (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol, 4 (5): 491-6. [PMID:12692549]
6. Lefranc J, Schulze VK, Hillig RC, Briem H, Prinz F, Mengel A, Heinrich T, Balint J, Rengachari S, Irlbacher H et al.. (2020) Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor. J Med Chem, 63 (2): 601-612. DOI: 10.1021/acs.jmedchem.9b01460 [PMID:31859507]
7. Li J, Huang J, Jeong JH, Park SJ, Wei R, Peng J, Luo Z, Chen YT, Feng Y, Luo JL. (2014) Selective TBK1/IKKi dual inhibitors with anticancer potency. Int J Cancer, 134 (8): 1972-80. [PMID:24150799]
8. 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]
9. Ou YH, Torres M, Ram R, Formstecher E, Roland C, Cheng T, Brekken R, Wurz R, Tasker A, Polverino T et al.. (2011) TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Mol Cell, 41 (4): 458-70. [PMID:21329883]
10. Perrior TR, Newton GK, Stewart MR, Aqil R. (2012) Pyrimidine compounds as inhibitors of protein kinases ikk epsilon and/or tbk-1, processes for their preparation, and pharmaceutical compositions containing them. Patent number: WO2012010826. Assignee: Domainex Limited. Priority date: 19/07/2010. Publication date: 26/01/2012.
11. Reilly SM, Chiang SH, Decker SJ, Chang L, Uhm M, Larsen MJ, Rubin JR, Mowers J, White NM, Hochberg I et al.. (2013) An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice. Nat Med, 19 (3): 313-21. [PMID:23396211]
12. Sankar S, Chan H, Romanow WJ, Li J, Bates RJ. (2006) IKK-i signals through IRF3 and NFkappaB to mediate the production of inflammatory cytokines. Cell Signal, 18 (7): 982-93. [PMID:16199137]
13. Thomson DW, Poeckel D, Zinn N, Rau C, Strohmer K, Wagner AJ, Graves AP, Perrin J, Bantscheff M, Duempelfeld B et al.. (2019) Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor. ACS Med Chem Lett, 10 (5): 780-785. DOI: 10.1021/acsmedchemlett.9b00027 [PMID:31097999]
14. 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]
IKK family: inhibitor of nuclear factor kappa B kinase subunit epsilon. Last modified on 03/11/2022. Accessed on 14/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2040.