serine/threonine kinase 3 | MST subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

serine/threonine kinase 3

Target id: 2219

Nomenclature: serine/threonine kinase 3

Abbreviated Name: MST2

Family: MST subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     serine/threonine kinase 3 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 491 8q22.2 STK3 serine/threonine kinase 3
Mouse - 497 15 B3.3 Stk3 serine/threonine kinase 3
Rat - 491 7 q22 Stk3 serine/threonine kinase 3
Previous and Unofficial Names
KRS1 | mess1
Database Links
BRENDA
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 Affinity Units Reference
staurosporine Hs Inhibition 9.4 pIC50 5
pIC50 9.4 (IC50 4.1x10-10 M) [5]
CEP-11981 Hs Inhibition 7.7 pIC50 6
pIC50 7.7 (IC50 2.1x10-8 M) [6]
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: 2,7

Key to terms and symbols Click column headers to sort
Target used in screen: MST2
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.7 pKd
lestaurtinib Hs Inhibitor Inhibition 8.6 pKd
sunitinib Hs Inhibitor Inhibition 7.3 pKd
neratinib Hs Inhibitor Inhibition 7.2 pKd
SU-14813 Hs Inhibitor Inhibition 7.2 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.8 pKd
midostaurin Hs Inhibitor Inhibition 6.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.5 pKd
bosutinib Hs Inhibitor Inhibition 6.4 pKd
dovitinib Hs Inhibitor Inhibition 6.3 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: MST2/MST2(STK3)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.1 4.5 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 1.3 0.0 1.0
midostaurin Hs Inhibitor Inhibition 1.9 3.0 0.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 2.7 5.0 0.0
K-252a Hs Inhibitor Inhibition 2.9 2.0 1.0
Gö 6976 Hs Inhibitor Inhibition 3.1 2.0 2.0
SB 218078 Hs Inhibitor Inhibition 3.2 10.0 12.0
PKR inhibitor Hs Inhibitor Inhibition 3.4 2.0 1.0
indirubin derivative E804 Hs Inhibitor Inhibition 4.8 4.0 1.0
JAK inhibitor I Hs Inhibitor Inhibition 5.4 14.0 4.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The Hippo pathway, in which MST1/2 kinase activity is key, has been shown to couple the cellular metabolic state and immune function of CD8α+ dendritic cells, in a mechanism that progammes this dendritic cell subset to present antigens to, and selectively prime CD8+ T cells [3]. In this way, output from the Hippo signalling pathway is able to induce cytotoxic T cell responses to viruses, bacteria and tumours. Manipulating this selective dendritic cell process has implications for cancer immunotherapy, and for treating immune disorders. It can be envisioned that pharmacological agents could be developed which are able to activate CD8α+ dendritic cells, shape the adaptive immune response, and prime anti-tumour T cells.
Immuno Process Associations
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0060215 primitive hemopoiesis IEA

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. 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. Du X, Wen J, Wang Y, Karmaus PWF, Khatamian A, Tan H, Li Y, Guy C, Nguyen TM, Dhungana Y et al.. (2018) Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature, 558 (7708): 141-145. [PMID:29849151]

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. Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM. (2009) Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J. Med. Chem., 52 (10): 3191-204. [PMID:19397322]

6. Hudkins RL, Becknell NC, Zulli AL, Underiner TL, Angeles TS, Aimone LD, Albom MS, Chang H, Miknyoczki SJ, Hunter K et al.. (2012) Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent. J. Med. Chem., 55 (2): 903-13. [PMID:22148921]

7. 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

MST subfamily: serine/threonine kinase 3. Last modified on 04/06/2018. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2219.