Top ▲

salt inducible kinase 1

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2197

Nomenclature: salt inducible kinase 1

Abbreviated Name: SIK

Family: QIK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 783 21q22.3 SIK1 salt inducible kinase 1
Mouse - 779 17 17.25 cM Sik1 salt inducible kinase 1
Rat - 776 20p12 Sik1 salt-inducible kinase 1
Previous and Unofficial Names Click here for help
Msk | myocardial SNF1-like kinase | protein kinase KID2 | Snf1lk | SNF1LK
Database Links Click here for help
Alphafold P57059 (Hs), Q60670 (Mm), Q9R1U5 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL6082 (Hs)
Ensembl Gene ENSG00000142178 (Hs), ENSMUSG00000024042 (Mm), ENSRNOG00000001189 (Rn)
Entrez Gene 150094 (Hs), 17691 (Mm), 59329 (Rn)
Human Protein Atlas ENSG00000142178 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:150094 (Hs), mmu:17691 (Mm), rno:59329 (Rn)
OMIM 605705 (Hs)
Pharos P57059 (Hs)
RefSeq Nucleotide NM_173354 (Hs), NM_010831 (Mm), NM_021693 (Rn)
RefSeq Protein NP_775490 (Hs), NP_034961 (Mm), NP_067725 (Rn)
UniProtKB P57059 (Hs), Q60670 (Mm), Q9R1U5 (Rn)
Wikipedia SIK1 (Hs)
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
HG-9-91-01 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.0 pIC50 1
⤷ pIC50 9.0 (IC50 9.2x10-10 M) [1]
GLPG3312 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 6
⤷ pIC50 8.7 (IC50 2x10-9 M) [6]
dasatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition >8.5 pIC50 5
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [5]
bosutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition >8.5 pIC50 5
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [5]
compound 2c [PMID: 24900538] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 7
⤷ pIC50 8.3 (IC50 5.5x10-9 M) [7]
ARN-3236 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 4
⤷ pIC50 7.7 (IC50 2.16x10-8 M) [4]
Description: In an in vitro enzymatic assay.
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: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: SIK
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 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: 3...
Key to terms and symbols Click column headers to sort
Target used in screen: SIK/nd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -2.0 -2.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 0.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.0 0.0
PDGF receptor tyrosine kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 4.0 5.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 4.0 2.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 8.0 2.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 24.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 18.0 8.0
CGP74514A Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.0 0.0
Syk inhibitor Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 24.0 11.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

Show »

1. Clark K, MacKenzie KF, Petkevicius K, Kristariyanto Y, Zhang J, Choi HG, Peggie M, Plater L, Pedrioli PG, McIver E et al.. (2012) Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci USA, 109 (42): 16986-91. [PMID:23033494]

2. 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]

3. 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]

4. Lombardi MS, Gilliéron C, Dietrich D, Gabay C. (2016) SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol, 99 (5): 711-21. [PMID:26590148]

5. Ozanne J, Prescott AR, Clark K. (2015) The clinically approved drugs dasatinib and bosutinib induce anti-inflammatory macrophages by inhibiting the salt-inducible kinases. Biochem J, 465 (2): 271-9. [PMID:25351958]

6. Temal-Laib T, Peixoto C, Desroy N, De Lemos E, Bonnaterre F, Bienvenu N, Picolet O, Sartori E, Bucher D, López-Ramos M et al.. (2024) Optimization of Selectivity and Pharmacokinetic Properties of Salt-Inducible Kinase Inhibitors that Led to the Discovery of Pan-SIK Inhibitor GLPG3312. J Med Chem, 67 (1): 380-401. [PMID:38147525]

7. Wang T, Lamb ML, Block MH, Davies AM, Han Y, Hoffmann E, Ioannidis S, Josey JA, Liu ZY, Lyne PD et al.. (2012) Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett, 3 (9): 705-9. [PMID:24900538]

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

QIK subfamily: salt inducible kinase 1. Last modified on 02/04/2024. Accessed on 07/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2197.