interleukin 1 receptor associated kinase 1 | Interleukin-1 receptor-associated kinase (IRAK) family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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interleukin 1 receptor associated kinase 1

  Target has curated data in GtoImmuPdb

Target id: 2042

Nomenclature: interleukin 1 receptor associated kinase 1

Abbreviated Name: IRAK1

Family: Interleukin-1 receptor-associated kinase (IRAK) 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 - 682 Xq28 IRAK1 interleukin 1 receptor associated kinase 1
Mouse - 750 X A7.3 Irak1 interleukin-1 receptor-associated kinase 1
Rat - 710 X q37 Irak1 interleukin-1 receptor-associated kinase 1
Previous and Unofficial Names
pelle | Plpk | interleukin-1 receptor-associated kinase 1
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.1

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 Parameter Reference
compound 1 [WO2012007375] Hs Inhibition 7.3 pIC50 2
pIC50 7.3 (IC50 5.5x10-8 M) [2]
IRAK-1/4 inhibitor Hs Inhibition 6.5 pIC50 5
pIC50 6.5 (IC50 3x10-7 M) [5]
Takinib Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 3.9x10-7 M) [6]
compound 7 [WO2012007375] Hs Inhibition 6.0 pIC50 2
pIC50 6.0 (IC50 9.83x10-7 M) [2]
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: 3,7

Key to terms and symbols Click column headers to sort
Target used in screen: IRAK1
Ligand Sp. Type Action Affinity Parameter
lestaurtinib Hs Inhibitor Inhibition 8.2 pKd
tamatinib Hs Inhibitor Inhibition 8.0 pKd
sunitinib Hs Inhibitor Inhibition 7.8 pKd
SU-14813 Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.3 pKd
KW-2449 Hs Inhibitor Inhibition 7.3 pKd
crizotinib Hs Inhibitor Inhibition 7.3 pKd
gefitinib Hs Inhibitor Inhibition 7.2 pKd
AST-487 Hs Inhibitor Inhibition 6.9 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: IRAK1/IRAK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SU6656 Hs Inhibitor Inhibition 5.6 9.0 0.0
K-252a Hs Inhibitor Inhibition 5.8 1.0 0.0
Gö 6976 Hs Inhibitor Inhibition 6.4 47.0 44.0
staurosporine Hs Inhibitor Inhibition 7.5 5.5 -0.5
SU11652 Hs Inhibitor Inhibition 14.1 9.0 0.0
Syk inhibitor Hs Inhibitor Inhibition 14.2 1.0 15.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 14.5 1.0 -1.0
IRAK-1/4 inhibitor Hs Inhibitor Inhibition 15.0 11.0 16.0
dorsomorphin Hs Inhibitor Inhibition 15.3 23.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 16.9 8.0 16.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 8 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS
GO:0034134 toll-like receptor 2 signaling pathway IMP
GO:0034142 toll-like receptor 4 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0045087 innate immune response IBA
GO:0060337 type I interferon signaling pathway IMP
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS
GO:0034134 toll-like receptor 2 signaling pathway IMP
GO:0034142 toll-like receptor 4 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 6 GO processes
GO:0001959 regulation of cytokine-mediated signaling pathway IMP
GO:0019221 cytokine-mediated signaling pathway IBA
GO:0032481 positive regulation of type I interferon production IMP
GO:0060337 type I interferon signaling pathway IMP
GO:0070498 interleukin-1-mediated signaling pathway IMP
GO:0070555 response to interleukin-1 IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes
GO:0002224 toll-like receptor signaling pathway TAS
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS
GO:0034134 toll-like receptor 2 signaling pathway IMP
GO:0034142 toll-like receptor 4 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell IMP
Clinically-Relevant Mutations and Pathophysiology
Disease:  Pediatric systemic lupus erythematosus
Synonyms: Systemic lupus erythematosus [Disease Ontology: DOID:9074]
Disease Ontology: DOID:9074
Orphanet: ORPHA93552

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. Arora N, Chen S, Hermann JC, KuglstatterA, Labadie SS, Lin CJJ, Lucas MC, Moore AG, Papp E, Talamas FX et al.. (2012) Pyrazolo [1, 5a] pyrimidine and thieno [3, 2b] pyrimidine derivatives as irak4 modulators. Patent number: WO2012007375. Assignee: F. Hoffmann-La Roche Ag. Priority date: 13/11/2015. Publication date: 19/01/2012.

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. 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]

5. Powers JP, Li S, Jaen JC, Liu J, Walker NP, Wang Z, Wesche H. (2006) Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4. Bioorg. Med. Chem. Lett., 16 (11): 2842-5. [PMID:16563752]

6. 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]

7. 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

Interleukin-1 receptor-associated kinase (IRAK) family: interleukin 1 receptor associated kinase 1. Last modified on 23/08/2017. Accessed on 25/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2042.