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SIK family kinase 3

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2199

Nomenclature: SIK family kinase 3

Abbreviated Name: QSK

Family: QIK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1321 11q23.3 SIK3 SIK family kinase 3
Mouse - 1311 9 A5.2 Sik3 SIK family kinase 3
Database Links Click here for help
Alphafold Q9Y2K2 (Hs), Q6P4S6 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL6149 (Hs)
Ensembl Gene ENSG00000160584 (Hs), ENSMUSG00000034135 (Mm)
Entrez Gene 23387 (Hs), 70661 (Mm)
Human Protein Atlas ENSG00000160584 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:23387 (Hs), mmu:70661 (Mm)
OMIM 614776 (Hs)
Pharos Q9Y2K2 (Hs)
RefSeq Nucleotide NM_025164 (Hs), NM_027498 (Mm)
RefSeq Protein NP_079440 (Hs), NP_081774 (Mm)
UniProtKB Q9Y2K2 (Hs), Q6P4S6 (Mm)
Wikipedia SIK3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Salt-Inducible Kinase 3 in complex with an inhibitor
PDB Id:  8OKU
Ligand:  GLPG3312
Resolution:  3.1Å
Species:  Human
References:  7
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
GLPG3970 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 – 11.0 pIC50 4
⤷ pIC50 8.0 – 11.0 (IC50 1x10-8 – 1x10-11 M) [4]
GLPG3312 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.2 pIC50 7
⤷ pIC50 9.2 (IC50 6x10-10 M) [7]
ARN-3236 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 5
⤷ pIC50 8.2 (IC50 6.6x10-9 M) [5]
Description: In an in vitro enzymatic assay.
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 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 9.6x10-9 M) [1]
dasatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 6
⤷ pIC50 8.0 (IC50 1x10-8 M) [6]
bosutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 6
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [6]
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: QSK
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Inhibition of SIK2 and SIK3 to promote macrophage switch to a 'regulatory'-like phenotype that favours resolution of inflammation is considered a potential therapeutic strategy for the treatment of chronic inflammatory diseases [2,6].

References

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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. Darling NJ, Toth R, Arthur JS, Clark K. (2017) Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages. Biochem J, 474 (4): 521-537. [PMID:27920213]

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. Desroy N, Joncour Am, Peixoto C, Temal-Laiob T, Tirera A, Bucher D, Amantini D, De Vos SIJ, Brys RCX. (2019) Novel compounds and pharmaceutical compositions thereof for the treatment of diseases. Patent number: WO2019238424A1. Assignee: Galapagos Nv. Priority date: 15/06/2018. Publication date: 19/12/2019.

5. 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]

6. 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]

7. 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]

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: SIK family kinase 3. Last modified on 02/04/2024. Accessed on 10/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2199.