MET proto-oncogene, receptor tyrosine kinase | Type X RTKs: HGF (hepatocyte growth factor) receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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MET proto-oncogene, receptor tyrosine kinase

  Target has curated data in GtoImmuPdb

Target id: 1815

Nomenclature: MET proto-oncogene, receptor tyrosine kinase

Abbreviated Name: MET

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 1390 7q31 MET MET proto-oncogene, receptor tyrosine kinase
Mouse 1 1379 6 A2 Met met proto-oncogene
Rat 1 1382 4q21 Met MET proto-oncogene
Previous and Unofficial Names
RCCP2 | HGF/SF receptor | scatter factor receptor | c-Met | HGF receptor | Par4 | hepatocyte growth factor receptor | mesenchymal-epithelial transition factor (c-Met) receptor | MET proto-oncogene
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  x-ray structure of c-Met with inhibitor.
PDB Id:  2RFN
Ligand:  AM7
Resolution:  2.5Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR C-MET
PDB Id:  1R1W
Resolution:  1.8Å
Species:  Human
References:  34
Image of receptor 3D structure from RCSB PDB
Description:  Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors.
PDB Id:  4R1V
Ligand:  tepotinib
Resolution:  1.2Å
Species:  Human
References:  15
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of c-Met in complex with triazolopyridazine inhibitor 2.
PDB Id:  4DEG
Ligand:  AMG-337
Resolution:  2.0Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of c-Met in complex with LY2801653 (merestinib).
PDB Id:  4EEV
Ligand:  merestinib
Resolution:  1.8Å
Species:  Human
References:  43
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
hepatocyte growth factor {Sp: Human}

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
SGX-523 Hs Inhibition 9.7 pKd 14
pKd 9.7 (Kd 1.9x10-10 M) [14]
PHA-665752 Hs Inhibition 9.6 pKd 14
pKd 9.6 (Kd 2.7x10-10 M) [14]
foretinib Hs Inhibition 8.9 pKd 14
pKd 8.9 (Kd 1.4x10-9 M) [14]
crizotinib Hs Inhibition 8.7 pKi 12
pKi 8.7 (Ki 2x10-9 M) [12]
merestinib Hs Inhibition 8.7 pKi 43
pKi 8.7 (Ki 2x10-9 M) [43]
PHA-665752 Hs Inhibition 8.4 pKi 10
pKi 8.4 (Ki 4x10-9 M) [10]
tivantinib Hs Inhibition 6.4 pKi 27
pKi 6.4 (Ki 3.55x10-7 M) [27]
tanespimycin Hs Inhibition 18.0 pIC50 37
pIC50 18.0 [37]
Description: Measuring downstream uPA-plasmin inhibition.
capmatinib Hs Inhibition 9.9 pIC50 24
pIC50 9.9 (IC50 1.3x10-10 M) [24]
foretinib Hs Inhibition 9.3 – 9.4 pIC50 23,28
pIC50 9.3 – 9.4 (IC50 5x10-10 – 4x10-10 M) [23,28]
ensartinib Hs Inhibition 9.1 pIC50 25
pIC50 9.1 (IC50 7.4x10-10 M) [25]
Description: Result from DiscoveRx KINOMEscan® selectivity screen.
crizotinib Hs Inhibition 9.1 pIC50 38
pIC50 9.1 (IC50 7.8x10-10 M) [38]
cabozantinib Hs Inhibition 8.9 pIC50 42
pIC50 8.9 (IC50 1.3x10-9 M) [42]
MK-2461 Hs Inhibition 8.6 pIC50 30
pIC50 8.6 (IC50 2.5x10-9 M) [30]
altiratinib Hs Inhibition 8.6 pIC50 16
pIC50 8.6 (IC50 2.7x10-9 M) [16]
tepotinib Hs Inhibition 8.5 pIC50 4
pIC50 8.5 (IC50 3x10-9 M) [4]
Description: Measured in a flash-plate assay using recombinant human c-Met kinase domain and a biotinylated peptide substrate.
BMS-777607 Hs Inhibition 8.4 pIC50 36
pIC50 8.4 (IC50 3.9x10-9 M) [36]
SGX-523 Hs Inhibition 8.4 pIC50 7
pIC50 8.4 (IC50 4x10-9 M) [7]
merestinib Hs Inhibition 8.3 pIC50 43
pIC50 8.3 (IC50 4.7x10-9 M) [43]
Description: Inhibition of in vitro biochemical activity by EMD Millipore assay.
AMG-337 Hs Inhibition 8.3 pIC50 6
pIC50 8.3 (IC50 5x10-9 M) [6]
Description: Biochemically assessed value.
savolitinib Hs Inhibition 8.3 pIC50 20
pIC50 8.3 (IC50 5x10-9 M) [20]
compound 1o [PMID: 24210504] Hs Inhibition 8.1 pIC50 9
pIC50 8.1 (IC50 8x10-9 M) [9]
SU11274 Hs Inhibition 8.0 pIC50 39
pIC50 8.0 (IC50 1x10-8 M) [39]
Description: Assay used a GST fusion with the cytoplasmic domain of human Met.
compound 27 [PMID: 21123062] Hs Inhibition 8.0 pIC50 40
pIC50 8.0 (IC50 1x10-8 M) [40]
golvatinib Hs Inhibition 7.8 pIC50 29
pIC50 7.8 (IC50 1.4x10-8 M) [29]
Description: Measured as inhibition of c-MET phosphorylation in MKN45 cells
compound 19a [PMID: 30503936] Hs Inhibition 7.8 pIC50 33
pIC50 7.8 (IC50 1.5x10-8 M) [33]
AM7 Hs Inhibition 7.8 pIC50 2
pIC50 7.8 (IC50 1.7x10-8 M) [2]
sitravatinib Hs Inhibition 7.7 pIC50 31
pIC50 7.7 (IC50 2x10-8 M) [31]
Description: In a biochemical enzyme activity assay.
compound R-16 [PMID: 21967808] Hs Inhibition 7.6 pIC50 26
pIC50 7.6 (IC50 2.4x10-8 M) [26]
glesatinib Hs Inhibition 7.5 pIC50 11
pIC50 7.5 (IC50 2.9x10-8 M) [11]
compound 16 [PMID: 18945615] Hs Inhibition 7.1 pIC50 35
pIC50 7.1 (IC50 8.5x10-8 M) [35]
compound 8i [PMID: 22765894] Hs Inhibition 6.3 pIC50 44
pIC50 6.3 (IC50 4.63x10-7 M) [44]
RIPK3 inhibitor 18 Hs Inhibition 6.0 pIC50 18
pIC50 6.0 (IC50 1.1x10-6 M) [18]
alectinib Hs Inhibition <5.3 pIC50 21
pIC50 <5.3 (IC50 >5x10-6 M) [21]
Inhibitor Comments
Tepotinib was shown to have an IC50 of <1nM in an in vitro study with recombinant human MET [15]. Tanespimycin is reported as a femtomolar inhibitor of MET-induced urokinase plasminogen activation (uPA) pathway [37].
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
emibetuzumab Hs Binding >10.0 pKd 13
pKd >10.0 (Kd <1x10-10 M) [13]
Description: binding constant for hMET extracellular domain measured using proprietary BIACore® technology
onartuzumab Hs Binding 8.4 pIC50 19,22
pIC50 8.4 (IC50 4.3x10-9 M) [19,22]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GE-137 Hs Binding 8.5 pKd 8
pKd 8.5 (Kd 3x10-9 M) [8]
Description: In vitro fluorescence polarization 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: 14,41

Key to terms and symbols Click column headers to sort
Target used in screen: MET
Ligand Sp. Type Action Value Parameter
SGX-523 Hs Inhibitor Inhibition 9.7 pKd
PHA-665752 Hs Inhibitor Inhibition 9.6 pKd
foretinib Hs Inhibitor Inhibition 8.9 pKd
crizotinib Hs Inhibitor Inhibition 8.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.8 pKd
staurosporine Hs Inhibitor Inhibition 6.7 pKd
tamatinib Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.5 pKd
cediranib Hs Inhibitor Inhibition 6.4 pKd
Target used in screen: MET(M1250T)
Ligand Sp. Type Action Value Parameter
crizotinib Hs Inhibitor Inhibition 9.3 pKd
PHA-665752 Hs Inhibitor Inhibition 9.2 pKd
SGX-523 Hs Inhibitor Inhibition 9.1 pKd
foretinib Hs Inhibitor Inhibition 9.0 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.2 pKd
AST-487 Hs Inhibitor Inhibition 7.0 pKd
staurosporine Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Hs Inhibitor Inhibition 6.7 pKd
tamatinib Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.3 pKd
Target used in screen: MET(Y1235D)
Ligand Sp. Type Action Value Parameter
foretinib Hs Inhibitor Inhibition 9.1 pKd
PHA-665752 Hs Inhibitor Inhibition 9.1 pKd
crizotinib Hs Inhibitor Inhibition 8.8 pKd
SGX-523 Hs Inhibitor Inhibition 8.4 pKd
lestaurtinib Hs Inhibitor Inhibition 7.4 pKd
staurosporine Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.7 pKd
tozasertib Hs Inhibitor Inhibition 6.4 pKd
cediranib Hs Inhibitor Inhibition 6.3 pKd
midostaurin 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: 1,17

Key to terms and symbols Click column headers to sort
Target used in screen: Met/c-MET
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SU11274 Hs Inhibitor Inhibition 1.2 2.0 0.0
staurosporine Hs Inhibitor Inhibition 32.7 4.0 1.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 40.4 3.0 0.0
K-252a Hs Inhibitor Inhibition 53.2 6.0 13.0
PDGF RTK inhibitor Hs Inhibitor Inhibition 60.4 28.0 4.0
GSK-3beta inhibitor I Hs Inhibitor Inhibition 64.2 141.0 95.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 70.0 118.0 97.0
tozasertib Hs Inhibitor Inhibition 70.9
erlotinib Hs Inhibitor Inhibition 71.4
Cdk2 inhibitor III Hs Inhibitor Inhibition 73.2 122.0 85.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
The leucine-rich repeat (LRR)-containing protein InlB of Listeria monocytogenes is reported to mediate bacterial entry in to non-phagocytic host cells by binding to the MET proto-oncogene, receptor tyrosine kinase (MET, or hepatocyte growth factor receptor, HGFR) [3]. Tanespimycin (a potent inhibitor of MET [37], in addition to Hsp90) has reported efficacy against intracellular infection of non-phagocytic cells by L. monocytogenes [32].
Immuno Process Associations
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes
GO:0035635 entry of bacterium into host cell TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006909 phagocytosis IBA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Pediatric hepatocellular carcinoma
Disease Ontology: DOID:684
OMIM: 114550
Orphanet: ORPHA33402
Disease:  Renal cell carcinoma, papillary, 1; RCCP1
Synonyms: Hereditary papillary renal cell carcinoma [Orphanet: ORPHA47044]
Papillary renal cell carcinoma [Disease Ontology: DOID:4465]
Disease Ontology: DOID:4465
OMIM: 605074
Orphanet: ORPHA47044

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. Bellon SF, Kaplan-Lefko P, Yang Y, Zhang Y, Moriguchi J, Rex K, Johnson CW, Rose PE, Long AM, O'Connor AB et al.. (2008) c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations. J. Biol. Chem., 283 (5): 2675-83. [PMID:18055465]

3. Bierne H, Cossart P. (2002) InlB, a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J. Cell. Sci., 115 (Pt 17): 3357-67. [PMID:12154067]

4. Bladt F, Faden B, Friese-Hamim M, Knuehl C, Wilm C, Fittschen C, Grädler U, Meyring M, Dorsch D, Jaehrling F et al.. (2013) EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors. Clin. Cancer Res., 19 (11): 2941-51. [PMID:23553846]

5. Bode CM, Boezio AA, Albrecht BK, Bellon SF, Berry L, Broome MA, Choquette D, Dussault I, Lewis RT, Lin MH et al.. (2012) Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors. Bioorg. Med. Chem. Lett., 22 (12): 4089-93. [PMID:22595176]

6. Boezio AA, Berry L, Albrecht BK, Bauer D, Bellon SF, Bode C, Chen A, Choquette D, Dussault I, Fang M et al.. (2009) Discovery and optimization of potent and selective triazolopyridazine series of c-Met inhibitors. Bioorg. Med. Chem. Lett., 19 (22): 6307-12. [PMID:19819693]

7. Buchanan SG, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ et al.. (2009) SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol. Cancer Ther., 8 (12): 3181-90. [PMID:19934279]

8. Burggraaf J, Kamerling IM, Gordon PB, Schrier L, de Kam ML, Kales AJ, Bendiksen R, Indrevoll B, Bjerke RM, Moestue SA et al.. (2015) Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat. Med., 21 (8): 955-61. [PMID:26168295]

9. Cho SY, Lee BH, Jung H, Yun CS, Ha JD, Kim HR, Chae CH, Lee JH, Seo HW, Oh KS. (2013) Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors. Bioorg. Med. Chem. Lett., 23 (24): 6711-6. [PMID:24210504]

10. Christensen JG, Schreck R, Burrows J, Kuruganti P, Chan E, Le P, Chen J, Wang X, Ruslim L, Blake R et al.. (2003) A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res., 63 (21): 7345-55. [PMID:14612533]

11. Claridge S, Raeppel F, Granger MC, Bernstein N, Saavedra O, Zhan L, Llewellyn D, Wahhab A, Deziel R, Rahil J et al.. (2008) Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases. Bioorg. Med. Chem. Lett., 18 (9): 2793-8. [PMID:18434145]

12. Cui JJ, Tran-Dubé M, Shen H, Nambu M, Kung PP, Pairish M, Jia L, Meng J, Funk L, Botrous I et al.. (2011) Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J. Med. Chem., 54 (18): 6342-63. [PMID:21812414]

13. Davies J, Liu L, Lu J, Vaillancourt PE, Wortinger MA, Zeng W. c-Met antibodies. Patent number: US8217148. Assignee: Eli Lilly And Company. Priority date: 21/11/2008. Publication date: 10/07/2012.

14. 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]

15. Dorsch D, Schadt O, Stieber F, Meyring M, Grädler U, Bladt F, Friese-Hamim M, Knühl C, Pehl U, Blaukat A. (2015) Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors. Bioorg. Med. Chem. Lett., 25 (7): 1597-602. [PMID:25736998]

16. Flynn DL, Kaufman MD, Smith BD. (2016) Inhibition of tumor cell interactions with the microenvironment resulting in a reduction in tumor growth and disease progression. Patent number: WO2016061231. Assignee: Deciphera Pharmaceuticals, Llc. Priority date: 14/10/2014. Publication date: 21/04/2016.

17. 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]

18. Hart AC, Abell L, Guo J, Mertzman ME, Padmanabha R, Macor JE, Chaudhry C, Lu H, O'Malley K, Shaw PJ et al.. (2019) Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage. ACS Medicinal Chemistry Letters, Article ASAP. DOI: 10.1021/acsmedchemlett.9b00065

19. Huang A, Schwall R, Yansura D. (2005) Monovalent antibody fragments useful as therapeutics. Patent number: US20050227324 A1. Assignee: Genentech, Inc.. Priority date: 19/12/2003. Publication date: 13/10/2005.

20. Jia H, Dai G, Weng J, Zhang Z, Wang Q, Zhou F, Jiao L, Cui Y, Ren Y, Fan S et al.. (2014) Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J. Med. Chem., 57 (18): 7577-89. [PMID:25148209]

21. Kinoshita K, Asoh K, Furuichi N, Ito T, Kawada H, Hara S, Ohwada J, Miyagi T, Kobayashi T, Takanashi K et al.. (2012) Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802). Bioorg. Med. Chem., 20 (3): 1271-80. [PMID:22225917]

22. Kong-Beltran M, Wickramasinghe DM. (2009) Methods and compositions for modulating hyperstabilized c-met. Patent number: US7615529 B2. Assignee: Genentech, Inc.. Priority date: 05/01/2016. Publication date: 10/11/2009.

23. Li S, Huang Q, Liu Y, Zhang X, Liu S, He C, Gong P. (2013) Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety. Eur J Med Chem, 64: 62-73. [PMID:23644189]

24. Liu X, Wang Q, Yang G, Marando C, Koblish HK, Hall LM, Fridman JS, Behshad E, Wynn R, Li Y et al.. (2011) A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin. Cancer Res., 17 (22): 7127-38. [PMID:21918175]

25. Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. (2011) Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res., 71 (14): 4920-31. [PMID:21613408]

26. Milkiewicz KL, Aimone LD, Albom MS, Angeles TS, Chang H, Grobelny JV, Husten J, Losardo C, Miknyoczki S, Murthy S et al.. (2011) Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group. Bioorg. Med. Chem., 19 (21): 6274-84. [PMID:21967808]

27. Munshi N, Jeay S, Li Y, Chen CR, France DS, Ashwell MA, Hill J, Moussa MM, Leggett DS, Li CJ. (2010) ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity. Mol. Cancer Ther., 9 (6): 1544-53. [PMID:20484018]

28. Musumeci F, Radi M, Brullo C, Schenone S. (2012) Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors. J. Med. Chem., 55 (24): 10797-822. [PMID:23098265]

29. Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H. (2010) E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci., 101 (1): 210-5. [PMID:19832844]

30. 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]

31. Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. (2016) Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget, 7 (4): 4093-109. [PMID:26675259]

32. Puthiyakunnon S, He X, Boddu S, Huang SH, Cao H. (2017) C-Met Inhibitors are Potential Novel Therapeutic Agents Against Listeria monocytogenes Infection Through Blocking the Bacteria Entry into Nonphagocytic Cells. Curr Top Med Chem, 17 (3): 278-289. [PMID:27572078]

33. 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]

34. Schiering N, Knapp S, Marconi M, Flocco MM, Cui J, Perego R, Rusconi L, Cristiani C. (2003) Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc. Natl. Acad. Sci. U.S.A., 100 (22): 12654-9. [PMID:14559966]

35. Schlapbach A, Feifel R, Hawtin S, Heng R, Koch G, Moebitz H, Revesz L, Scheufler C, Velcicky J, Waelchli R et al.. (2008) Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Bioorg. Med. Chem. Lett., 18 (23): 6142-6. [PMID:18945615]

36. 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]

37. Shen Y, Xie Q, Norberg M, Sausville E, Vande Woude G, Wenkert D. (2005) Geldanamycin derivative inhibition of HGF/SF-mediated Met tyrosine kinase receptor-dependent urokinase-plasminogen activation. Bioorg. Med. Chem., 13 (16): 4960-71. [PMID:15978816]

38. Slavish PJ, Price JE, Jiang Q, Cui X, Morris SW, Webb TR. (2011) Synthesis of an aryloxy oxo pyrimidinone library that displays ALK-selective inhibition. Bioorg. Med. Chem. Lett., 21 (15): 4592-6. [PMID:21708465]

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How to cite this page

Type X RTKs: HGF (hepatocyte growth factor) receptor family: MET proto-oncogene, receptor tyrosine kinase. Last modified on 17/05/2019. Accessed on 26/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1815.