macrophage stimulating 1 receptor | Type X RTKs: HGF (hepatocyte growth factor) receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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macrophage stimulating 1 receptor

  Target has curated data in GtoImmuPdb

Target id: 1816

Nomenclature: macrophage stimulating 1 receptor

Abbreviated Name: Ron

Family: Type X RTKs: HGF (hepatocyte growth factor) receptor family

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 1 1400 3p21 MST1R macrophage stimulating 1 receptor
Mouse 1 1378 9 F1 Mst1r macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
Rat - 1373 8q32 Mst1r macrophage stimulating 1 receptor
Previous and Unofficial Names
CD136 | PTK8 | protein tyrosine kinase 8 | friend virus susceptibility 2 | Fv2 | macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  RON in complex with ligand AMP-PNP
PDB Id:  3PLS
Ligand:  AMP-PNP
Resolution:  2.24Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Sema-PSI extracellular domains of human RON receptor tyrosine kinase
PDB Id:  4FWW
Resolution:  1.85Å
Species:  Human
References:  3
Enzyme Reaction
EC Number: 2.7.10.1

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 Parameter Reference
BMS-777607 Hs Inhibition 8.7 pIC50 8
pIC50 8.7 (IC50 1.8x10-9 M) [8]
compound 19a [PMID: 30503936] Hs Inhibition 8.5 pIC50 7
pIC50 8.5 (IC50 2.9x10-9 M) [7]
MK-2461 Hs Inhibition 8.1 pIC50 6
pIC50 8.1 (IC50 7x10-9 M) [6]
merestinib Hs Inhibition 7.9 pIC50 11
pIC50 7.9 (IC50 1.2x10-8 M) [11]
Description: Inhibition of in vitro biochemical activity by EMD Millipore assay.
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: 4,10

Key to terms and symbols Click column headers to sort
Target used in screen: MST1R
Ligand Sp. Type Action Affinity Parameter
foretinib Hs Inhibitor Inhibition 8.5 pKd
crizotinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 6.4 pKd
tamatinib Hs Inhibitor Inhibition 6.3 pKd
AST-487 Hs Inhibitor Inhibition 6.3 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.2 pKd
KW-2449 Hs Inhibitor Inhibition 6.1 pKd
tozasertib Hs Inhibitor Inhibition 5.9 pKd
PHA-665752 Hs Inhibitor Inhibition 5.7 pKd
PD-173955 Hs Inhibitor Inhibition 5.6 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: 2,5

Key to terms and symbols Click column headers to sort
Target used in screen: Ron/RON(MSTR1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 44.7 14.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 56.0 7.0 2.0
PKR inhibitor Hs Inhibitor Inhibition 70.2 60.0 11.0
PD 158780 Hs Inhibitor Inhibition 73.9 88.0 66.0
PD 169316 Hs Inhibitor Inhibition 76.8 90.0 90.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 80.0 67.0 7.0
p38 MAP kinase inhibitor III Hs Inhibitor Inhibition 81.3 98.0 83.0
IKK-2 inhibitor IV Hs Inhibitor Inhibition 81.7 73.0 56.0
K-252a Hs Inhibitor Inhibition 82.3 33.0 3.0
PQ401 Hs Inhibitor Inhibition 82.4 102.0 78.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The role of RON in immuno-oncology is reviewed in [1].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0005011 macrophage colony-stimulating factor receptor activity TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045087 innate immune response IEA

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. 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]

3. Chao KL, Tsai IW, Chen C, Herzberg O. (2012) Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase. PLoS ONE, 7 (7): e41912. [PMID:22848655]

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. 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]

6. Pan BS, Chan GK, Chenard M, Chi A, Davis LJ, Deshmukh SV, Gibbs JB, Gil S, Hang G, Hatch H et al.. (2010) MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res., 70 (4): 1524-33. [PMID:20145145]

7. Qi B, Yang Y, Gong G, He H, Yue X, Xu X, Hu Y, Li J, Chen T, Wan X et al.. (2019) Discovery of N1-(4-((7-(3-(4-ethylpiperazin-1-yl)propoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-N3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)urea as a multi-tyrosine kinase inhibitor for drug-sensitive and drug-resistant cancers treatment. Eur J Med Chem, 163: 10-27. [PMID:30503936]

8. Schroeder GM, An Y, Cai ZW, Chen XT, Clark C, Cornelius LA, Dai J, Gullo-Brown J, Gupta A, Henley B et al.. (2009) Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem., 52 (5): 1251-4. [PMID:19260711]

9. Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP. (2010) The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry, 49 (37): 7972-4. [PMID:20726546]

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. Yan SB, Peek VL, Ajamie R, Buchanan SG, Graff JR, Heidler SA, Hui YH, Huss KL, Konicek BW, Manro JR et al.. (2013) LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs, 31 (4): 833-44. [PMID:23275061]

How to cite this page

Type X RTKs: HGF (hepatocyte growth factor) receptor family: macrophage stimulating 1 receptor. Last modified on 16/01/2019. Accessed on 19/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1816.