inhibitor of nuclear factor kappa B kinase subunit epsilon | IKK family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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inhibitor of nuclear factor kappa B kinase subunit epsilon

Target id: 2040

Nomenclature: inhibitor of nuclear factor kappa B kinase subunit epsilon

Abbreviated Name: IKK-epsilon

Family: IKK family

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   GtoImmuPdb view: ON :     inhibitor of nuclear factor kappa B kinase subunit epsilon has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 716 1q31 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
Previous and Unofficial Names
IKKE | IKKepsilon | IKKI | Inducible I kappa-B kinase | inhibitor of kappa light polypeptide gene enhancer in B-cells | inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.10

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
Ligand Sp. Action Affinity Units Reference
SR8185 Hs Inhibition 8.5 pIC50 5
pIC50 8.5 (IC50 3x10-9 M) [5]
Description: In an enzyme assay.
MPI-0485520 Hs Inhibition 8.5 pIC50 8
pIC50 8.5 (IC50 3x10-9 M) [8]
Description: Using a Kinase Hotspot® assay.
compound 17d [PMID: 23099093] Hs Inhibition 7.5 pIC50 6
pIC50 7.5 (IC50 3x10-8 M) [6]
compound II [PMID: 21329883] Hs Inhibition 7.2 pIC50 7
pIC50 7.2 (IC50 5.9x10-8 M) [7]
Description: In a biochemical assay using purified recombinant enzyme.
MRT67307 Hs Inhibition 6.8 pIC50 2
pIC50 6.8 (IC50 1.6x10-7 M) [2]
amlexanox Hs Inhibition 5.7 – 6.0 pIC50 9
pIC50 5.7 – 6.0 (IC50 2x10-6 – 1x10-6 M) [9]
Description: Inhibition of substrate phosphorylation.
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: 3,11

Key to terms and symbols Click column headers to sort
Target used in screen: IKK-epsilon
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.3 pKd
lestaurtinib Hs Inhibitor Inhibition 8.0 pKd
tamatinib Hs Inhibitor Inhibition 7.9 pKd
bosutinib Hs Inhibitor Inhibition 7.3 pKd
midostaurin Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Hs Inhibitor Inhibition 6.5 pKd
fedratinib Hs Inhibitor Inhibition 6.4 pKd
dovitinib Hs Inhibitor Inhibition 6.3 pKd
SU-14813 Hs Inhibitor Inhibition 6.3 pKd
sunitinib Hs Inhibitor Inhibition 6.2 pKd
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

Key to terms and symbols Click column headers to sort
Target used in screen: nd/IKKe(IKBKE)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.3
K-252a Hs Inhibitor Inhibition 2.4
midostaurin Hs Inhibitor Inhibition 9.9
JAK3 inhibitor VI Hs Inhibitor Inhibition 14.9
Syk inhibitor Hs Inhibitor Inhibition 21.9
SB 218078 Hs Inhibitor Inhibition 23.9
JAK inhibitor I Hs Inhibitor Inhibition 25.4
PKR inhibitor Hs Inhibitor Inhibition 27.6
SU11652 Hs Inhibitor Inhibition 29.4
dovitinib Hs Inhibitor Inhibition 42.9
Displaying the top 10 most potent ligands  View all ligands in screen »
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 [4,10].

References

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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. 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. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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.

9. 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]

10. 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]

11. 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]

How to cite this page

IKK family: inhibitor of nuclear factor kappa B kinase subunit epsilon. Last modified on 23/05/2017. Accessed on 20/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2040.