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interleukin 1 receptor associated kinase 1

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Immunopharmacology Ligand 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

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 712 Xq28 IRAK1 interleukin 1 receptor associated kinase 1
Mouse - 710 X 37.61 cM Irak1 interleukin-1 receptor-associated kinase 1
Rat - 710 X q37 Irak1 interleukin-1 receptor-associated kinase 1
Previous and Unofficial Names Click here for help
pelle | Plpk | interleukin-1 receptor-associated kinase 1
Database Links Click here for help
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
belizatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKd 5
pKd 8.2 (Kd 5.7x10-9 M) [5]
Description: Binding affinity in vitro.
compound 1 [WO2012007375] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 2
pIC50 7.3 (IC50 5.5x10-8 M) [2]
IRAK-1/4 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.5 pIC50 6
pIC50 6.5 (IC50 3x10-7 M) [6]
Takinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.4 pIC50 7
pIC50 6.4 (IC50 3.9x10-7 M) [7]
compound 7 [WO2012007375] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.0 pIC50 2
pIC50 6.0 (IC50 9.83x10-7 M) [2]
DiscoveRx KINOMEscan® screen Click here for help
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: 3,8

Key to terms and symbols Click column headers to sort
Target used in screen: IRAK1
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product 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 Click here for help
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 9.0 0.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 5.8 1.0 0.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 47.0 44.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 5.5 -0.5
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 14.1 9.0 0.0
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 14.2 1.0 15.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 14.5 1.0 -1.0
IRAK-1/4 inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 15.0 11.0 16.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.3 23.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure 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 2 GO processes
GO:0045087 innate immune response IBA
GO:0060337 type I interferon signaling pathway IMP
Immuno Process:  Immune regulation
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
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 Click here for help
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. Lewis RT, Bode CM, Choquette DM, Potashman M, Romero K, Stellwagen JC, Teffera Y, Moore E, Whittington DA, Chen H et al.. (2012) The discovery and optimization of a novel class of potent, selective, and orally bioavailable anaplastic lymphoma kinase (ALK) inhibitors with potential utility for the treatment of cancer. J Med Chem, 55 (14): 6523-40. [PMID:22734674]

6. 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]

7. 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]

8. 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 04/09/2019. Accessed on 22/06/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2042.