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macrophage stimulating 1 receptor

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Immunopharmacology Ligand  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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1400 3p21.31 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 Click here for help
CD136 | PTK8 | protein tyrosine kinase 8 | friend virus susceptibility 2 | Fv2 | macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
Database Links Click here for help
Alphafold Q04912 (Hs), Q62190 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 2.130.10.10, 2.60.40.10
ChEMBL Target CHEMBL2689 (Hs), CHEMBL1795170 (Mm)
Ensembl Gene ENSG00000164078 (Hs), ENSMUSG00000032584 (Mm), ENSRNOG00000032618 (Rn)
Entrez Gene 4486 (Hs), 19882 (Mm), 300999 (Rn)
Human Protein Atlas ENSG00000164078 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:4486 (Hs), mmu:19882 (Mm), rno:300999 (Rn)
OMIM 600168 (Hs)
Pharos Q04912 (Hs)
RefSeq Nucleotide NM_001244937 (Hs), NM_009074 (Mm), NM_001106855 (Rn)
RefSeq Protein NP_002438 (Hs), NP_033100 (Mm), NP_001100325 (Rn)
UniProtKB Q04912 (Hs), Q62190 (Mm)
Wikipedia MST1R (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
macrophage stimulating protein 1 {Sp: Human}

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
BMS-777607 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 8
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [8]
compound 19a [PMID: 30503936] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 7
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [7]
MK-2461 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 6
⤷ pIC50 8.1 (IC50 7x10-9 M) [6]
merestinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand 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.
compound 8i [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 12
⤷ pIC50 6.9 (IC50 1.24x10-7 M) [12]
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: MST1R
Ligand Sp. Type Action Value Parameter
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
PHA-665752 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure 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 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: 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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.7 14.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 56.0 7.0 2.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 70.2 60.0 11.0
PD 158780 Small molecule or natural product Hs Inhibitor Inhibition 73.9 88.0 66.0
PD 169316 Small molecule or natural product Hs Inhibitor Inhibition 76.8 90.0 90.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 80.0 67.0 7.0
p38 MAP kinase inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 81.3 98.0 83.0
IKK-2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 81.7 73.0 56.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 82.3 33.0 3.0
PQ401 Small molecule or natural product 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
Immuno Process:  Inflammation

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]

12. You WK, Sennino B, Williamson CW, Falcón B, Hashizume H, Yao LC, Aftab DT, McDonald DM. (2011) VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 71 (14): 4758-68. [PMID:21613405]

How to cite this page

Type X RTKs: HGF (hepatocyte growth factor) receptor family: macrophage stimulating 1 receptor. Last modified on 24/04/2019. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1816.