salt inducible kinase 2 | QIK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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salt inducible kinase 2

target has curated data in GtoImmuPdb

Target id: 2198

Nomenclature: salt inducible kinase 2

Abbreviated Name: QIK

Family: QIK subfamily

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 - 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
Sik2 | SNF1-like kinase 2 | SNF1LK2 | salt-inducible kinase 2
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
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 Value Parameter Reference
ARN-3236 Hs Inhibition >9.0 pIC50 6
pIC50 >9.0 (IC50 <1x10-9 M) [6]
Description: In an in vitro enzymatic assay.
dasatinib Hs Inhibition >8.5 pIC50 7
pIC50 >8.5 (IC50 <3x10-9 M) [7]
bosutinib Hs Inhibition >8.5 pIC50 7
pIC50 >8.5 (IC50 <3x10-9 M) [7]
HG-9-91-01 Hs Inhibition 8.2 pIC50 2
pIC50 8.2 (IC50 6.6x10-9 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: 4,8

Key to terms and symbols Click column headers to sort
Target used in screen: SIK2
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 9.0 pKd
dasatinib Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.8 pKd
PD-173955 Hs Inhibitor Inhibition 7.6 pKd
bosutinib Hs Inhibitor Inhibition 7.5 pKd
tamatinib Hs Inhibitor Inhibition 7.1 pKd
fedratinib Hs Inhibitor Inhibition 7.0 pKd
crizotinib Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 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
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 Hs Inhibitor Inhibition 0.1
dasatinib Hs Inhibitor Inhibition 1.9
bosutinib Hs Inhibitor Inhibition 1.9
K-252a Hs Inhibitor Inhibition 4.0
midostaurin Hs Inhibitor Inhibition 11.7
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 16.1
vandetanib Hs Inhibitor Inhibition 17.6
dovitinib Hs Inhibitor Inhibition 25.5
sunitinib Hs Inhibitor Inhibition 27.8
GSK-3 inhibitor IX 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 [3,7].
General Comments
SIK2's involvement in mitotic spindle formation has promoted its consideration as a potential target for cancer therapy [5]. Inhibition of SIKs is proposed as a method of sensitizing cancer cells to other chemotherapeutic drugs [9].

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. 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. U.S.A., 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. 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]

6. 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]

7. 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]

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]

9. 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 23/05/2017. Accessed on 23/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2198.