component of inhibitor of nuclear factor kappa B kinase complex | IKK family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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component of inhibitor of nuclear factor kappa B kinase complex

  Target has curated data in GtoImmuPdb

Target id: 1989

Nomenclature: component of inhibitor of nuclear factor kappa B kinase complex

Abbreviated Name: IKK-alpha

Family: IKK family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 745 10q24-q25 CHUK component of inhibitor of nuclear factor kappa B kinase complex
Mouse - 719 19 C3 Chuk conserved helix-loop-helix ubiquitous kinase
Rat - 745 1 q54 Chuk conserved helix-loop-helix ubiquitous kinase
Previous and Unofficial Names
Chuk1 | conserved helix-loop-helix ubiquitous kinase | I-kappa-B kinase 1 | IkappaB kinase alpha | IkBKA | IKK1 | IKKA | IKKalpha | inhibitor of nuclear factor kappa-B kinase subunit alpha | NFKBIKA | nuclear factor NF-kappa-B inhibitor kinase alpha | TCF16
Database Links
BRENDA
ChEMBL Target
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 Value Parameter Reference
BAY 61-3606 Hs Inhibition 7.3 pKi 6
pKi 7.3 (Ki 4.5x10-8 M) [6]
compound 47 [PMID: 28737909] Hs Inhibition 6.2 pKi 2
pKi 6.2 (Ki 6.5x10-7 M) [2]
PHA-408 Hs Inhibition 4.8 pIC50 8
pIC50 4.8 (IC50 1.41x10-5 M) [8]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BMS-345541 Hs Negative 5.4 pIC50 3
pIC50 5.4 (IC50 4x10-6 M) [3]
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: 4,9

Key to terms and symbols Click column headers to sort
Target used in screen: IKK-alpha
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 8.1 pKd
AST-487 Hs Inhibitor Inhibition 7.4 pKd
tamatinib Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Hs Inhibitor Inhibition 6.7 pKd
sunitinib Hs Inhibitor Inhibition 6.3 pKd
SU-14813 Hs Inhibitor Inhibition 6.2 pKd
fedratinib Hs Inhibitor Inhibition 6.1 pKd
MLN-120B Hs Inhibitor Inhibition 6.0 pKd
PI-103 Hs Inhibitor Inhibition 5.8 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: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: IKKα/IKKA(CHUK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 36.5 2.0 3.0
staurosporine Hs Inhibitor Inhibition 40.3 5.5 1.0
PKR inhibitor Hs Inhibitor Inhibition 53.2 8.0 1.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 54.4 10.0 1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 60.3 5.0 0.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 72.0 90.0 86.0
aloisine A Hs Inhibitor Inhibition 77.6 90.0 81.0
Cdk4 inhibitor Hs Inhibitor Inhibition 81.5 89.0 71.0
fascaplysin Hs Inhibitor Inhibition 82.6 108.0 108.0
Flt-3 inhibitor Hs Inhibitor Inhibition 83.3 105.0 113.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [7].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 5 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0006954 inflammatory response TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0045087 innate immune response TAS
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 5 GO processes
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS
GO:0033209 tumor necrosis factor-mediated signaling pathway IBA
GO:0070498 interleukin-1-mediated signaling pathway TAS
GO:0071356 cellular response to tumor necrosis factor IDA
GO:1902741 positive regulation of interferon-alpha secretion IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 5 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cocoon syndrome
OMIM: 613630

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. Anthony NG, Baiget J, Berretta G, Boyd M, Breen D, Edwards J, Gamble C, Gray AI, Harvey AL, Hatziieremia S et al.. (2017) Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers. J. Med. Chem., 60 (16): 7043-7066. [PMID:28737909]

3. Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, McIntyre KW, Yang X, Iotzova VS, Clarke W, Strnad J et al.. (2003) BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J. Biol. Chem., 278 (3): 1450-6. [PMID:12403772]

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. 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]

6. Ho CM, Donovan-Banfield IZ, Tan L, Zhang T, Gray NS, Strang BL. (2016) Inhibition of IKKα by BAY61-3606 Reveals IKKα-Dependent Histone H3 Phosphorylation in Human Cytomegalovirus Infected Cells. PLoS ONE, 11 (3): e0150339. [PMID:26930276]

7. Huang WC, Hung MC. (2013) Beyond NF-κB activation: nuclear functions of IκB kinase α. J. Biomed. Sci., 20: 3. [PMID:23343355]

8. Mbalaviele G, Sommers CD, Bonar SL, Mathialagan S, Schindler JF, Guzova JA, Shaffer AF, Melton MA, Christine LJ, Tripp CS et al.. (2009) A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models. J. Pharmacol. Exp. Ther., 329 (1): 14-25. [PMID:19168710]

9. 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: component of inhibitor of nuclear factor kappa B kinase complex. Last modified on 27/03/2019. Accessed on 21/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1989.