Top ▲

salt inducible kinase 2

Click here for help

Target id: 2198

Nomenclature: salt inducible kinase 2

Abbreviated Name: QIK

Family: QIK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 926 11q23.1 SIK2 salt inducible kinase 2
Mouse - 931 9 A5.3 Sik2 salt inducible kinase 2
Rat - 914 8q24 Sik2 salt-inducible kinase 2
Previous and Unofficial Names Click here for help
Sik2 | SNF1-like kinase 2 | SNF1LK2 | salt-inducible kinase 2
Database Links Click here for help
Alphafold Q9H0K1 (Hs), Q8CFH6 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5699 (Hs)
Ensembl Gene ENSG00000170145 (Hs), ENSMUSG00000037112 (Mm), ENSRNOG00000043498 (Rn)
Entrez Gene 23235 (Hs), 235344 (Mm), 315649 (Rn)
Human Protein Atlas ENSG00000170145 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:23235 (Hs), mmu:235344 (Mm), rno:315649 (Rn)
OMIM 608973 (Hs)
Pharos Q9H0K1 (Hs)
RefSeq Nucleotide NM_015191 (Hs), NM_178710 (Mm)
RefSeq Protein NP_056006 (Hs), NP_848825 (Mm)
UniProtKB Q9H0K1 (Hs), Q8CFH6 (Mm)
Wikipedia SIK2 (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
GLPG3970 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 – 11.0 pIC50 5
⤷ pIC50 8.0 – 11.0 (IC50 1x10-8 – 1x10-11 M) [5]
GLPG3312 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 9
⤷ pIC50 9.1 (IC50 7x10-10 M) [9]
ARN-3236 Small molecule or natural product Click here for species-specific activity table Hs Inhibition >9.0 pIC50 7
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [7]
Description: In an in vitro enzymatic assay.
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 8
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [8]
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 8
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [8]
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 8.2 pIC50 2
⤷ pIC50 8.2 (IC50 6.6x10-9 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: 4,10
Key to terms and symbols Click column headers to sort
Target used in screen: SIK2
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.4 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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/SIK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.1
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.9
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.9
K-252a Small molecule or natural product Hs Inhibitor Inhibition 4.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 11.7
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 16.1
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 17.6
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 25.5
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 27.8
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 31.1
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 [3,8].
General Comments
SIK2's involvement in mitotic spindle formation has promoted its consideration as a potential target for cancer therapy [6]. Inhibition of SIKs is proposed as a method of sensitizing cancer cells to other chemotherapeutic drugs [11].

References

Show »

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. 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]

3. 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]

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. 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.

6. Du WQ, Zheng JN, Pei DS. (2016) The diverse oncogenic and tumor suppressor roles of salt-inducible kinase (SIK) in cancer. Expert Opin Ther Targets, 20 (4): 477-85. [PMID:26549013]

7. 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]

8. 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]

9. 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]

10. 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]

11. Zhou J, Alfraidi A, Zhang S, Santiago-O'Farrill JM, Yerramreddy Reddy VK, Alsaadi A, Ahmed AA, Yang H, Liu J, Mao W et al.. (2017) A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res, 23 (8): 1945-1954. [PMID:27678456]

How to cite this page

QIK subfamily: salt inducible kinase 2. Last modified on 02/04/2024. Accessed on 25/04/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2198.