Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNDSF4)

• DTT Name: Proto-oncogene c-Met (MET)
• Synonyms: Tyrosine-protein kinase Met; Scatter factor receptor; SF receptor; Met proto-oncogene tyrosine kinase; Hepatocyte growth factor receptor; HGF/SF receptor; HGF-SF receptor; HGF receptor; C-met; C-Met receptor tyrosine kinase
• Gene Name: MET
• DTT Type: Successful target; [1]
• Related Disease:
  Lung cancer [ICD-11: 2C25]
  Non-small cell lung cancer [ICD-11: 2C25]
  Thyroid cancer [ICD-11: 2D10]
• BioChemical Class: Kinase
• UniProt ID: MET_HUMAN
• TTD ID: T40474
• EC Number: EC 2.7.10.1
• Sequence:
  MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
  HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
  VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
  GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE
  FRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECIL
  TEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
  AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEF
  TTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFL
  LDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
  CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKK
  TRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVIT
  SISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
  AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVH
  EAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPV
  FKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
  LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQ
  IKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGS
  CRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHF
  NEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVL
  SLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKF
  VHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKF
  TTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCW
  HPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVD
  TRPASFWETS
• Function: Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Cytokine-cytokine receptor interaction (hsa04060)
  Endocytosis (hsa04144)
  PI3K-Akt signaling pathway (hsa04151)
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Bacterial invasion of epithelial cells (hsa05100)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Malaria (hsa05144)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Renal cell carcinoma (hsa05211)
  Melanoma (hsa05218)
  Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway: Sema4D mediated inhibition of cell attachment and migration (R-HSA-416550)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[2], [3]
Capmatinib	DMYCXKL	Non-small-cell lung cancer	2C25.Y	Approved	[4]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[1]
Tepotinib	DMUQ0E8	Non-small cell lung cancer	2C25	Approved	[5]

43 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25.Y	Phase 3	[6]
Beperminogene perplasmid	DM6RWBN	Critical limb ischemia	BD4Y	Phase 3	[7]
RG3638	DMTQJE0	Gastric adenocarcinoma	2B72	Phase 3	[8]
Savolitinib	DMALFKX	Renal cell carcinoma	2C90	Phase 3	[9]
Tivantinib	DMNVP8Q	Hepatocellular carcinoma	2C12.02	Phase 3	[10]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[8]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[11]
AMG 208	DMPQHOR	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
AMG 337	DMIOUEY	Clear cell sarcoma	2A60-2C35	Phase 2	[13]
APL-101	DMP0LST	Non-small cell lung cancer	2C25	Phase 2	[14]
CMX-2043	DMPSCVY	Cardiac disease	BA00-BE2Z	Phase 2	[15]
Emibetuzumab	DMT4MKF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
HM-5016504	DMLQDBH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
LY-2875358	DMQV1OU	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17], [18]
LY2801653	DM0KJDY	Biliary tract cancer	2C17	Phase 2	[19], [20]
SAR-125844	DMJ34G6	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
Telisotuzumab vedotin	DM8UCNK	Non-small-cell lung cancer	2C25.Y	Phase 2	[22]
XL880	DMHJTR2	Breast cancer	2C60-2C65	Phase 2	[23]
Anti-C-met CAR-T cells	DMV5H0S	Colorectal cancer	2B91.Z	Phase 1/2	[24]
BMS-777607	DMGM7QD	N. A.	N. A.	Phase 1/2	[25]
ChronSeal	DM90BUD	Fibrosis	GA14-GC01	Phase 1/2	[26]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[27]
Sym015	DM9B7Z5	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
ABBV-399	DMQGPRE	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
ABT-700	DMVLPRT	Advanced solid tumour	2A00-2F9Z	Phase 1	[28]
Altiratinib	DMUJCBT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[29], [3]
Autologous T Cells Expressing MET scFv CAR	DMZ763A	Melanoma	2C30	Phase 1	[30]
BPI-9016 M	DMNY0U5	Solid tumour/cancer	2A00-2F9Z	Phase 1	[31]
C-Met/PD-L1 CAR-T Cell	DMHBNKP	Hepatocellular carcinoma	2C12.02	Phase 1	[32]
CBT-101	DMOTLN4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
E-7050	DMDOCNW	Head and neck cancer	2D42	Phase 1	[33]
EMD-1204831	DM38JZU	Solid tumour/cancer	2A00-2F9Z	Phase 1	[34]
Hepapoietin	DMM7VOB	Liver disease	DB90-BD99	Phase 1	[35]
JNJ-38877605	DMDIPW8	Solid tumour/cancer	2A00-2F9Z	Phase 1	[36]
LY3164530	DM9RTXM	Advanced cancer	2A00-2F9Z	Phase 1	[37]
MK-8033	DMA1EDN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[38]
PF-4217903	DMU2A6D	Solid tumour/cancer	2A00-2F9Z	Phase 1	[39]
REGN5093	DM3720L	Non-small-cell lung cancer	2C25.Y	Phase 1	[40]
RXDX-106	DM6NVTR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[41]
Sgx523	DM3RSMF	Solid tumour/cancer	2A00-2F9Z	Phase 1	[42]
TPX-0022	DMC2IJN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[43]
TR1801-ADC	DMGC2AT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[44]
XL092	DM3LRAC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[45]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mteron-F1	DMCZW4Q	Mucositis	CA00	Preclinical	[46]
NPS-1034	DMOGRWB	Solid tumour/cancer	2A00-2F9Z	Preclinical	[47]

26 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(2-nitrophenethyl)-1H-pyrrolo[3,2-b]pyridine	DMR12KP	Discovery agent	N.A.	Investigative	[48]
1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine	DM8APLN	Discovery agent	N.A.	Investigative	[48]
1-benzyl-1H-pyrrolo[3,2-b]pyridine	DMEVSFY	Discovery agent	N.A.	Investigative	[48]
3-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine	DMN1DWF	Discovery agent	N.A.	Investigative	[48]
ALD-805	DMQXO5G	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
ALD-806	DMWBKH1	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
AM7	DMYVQFN	Discovery agent	N.A.	Investigative	[49]
Anti-cMET mab	DM2X1SG	Discovery agent	N.A.	Investigative	[8]
APS-3010	DM8DOBG	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
BAY-85-3474	DMW625B	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[50]
CMET Avimer polypeptides	DM6PFG0	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
DP-3590	DMFZML9	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
GE-137	DMB813H	Discovery agent	N.A.	Investigative	[51]
HuMax-cMet	DM8AG5R	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
LA-480	DMP1V8Y	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
mab 224G11	DM1ICOW	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PF-00614435	DMWL9CU	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PHA-665752	DMCGX9U	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PMID21123062C27	DMVPW1G	Discovery agent	N.A.	Investigative	[52]
PMID21967808CR-16	DMCOHKU	Discovery agent	N.A.	Investigative	[53]
PMID24210504C1o	DM4LEUT	Discovery agent	N.A.	Investigative	[54]
PRS-110	DMB923H	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
RP-1040	DMP2EDX	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
SU11274	DMASP9Z	Discovery agent	N.A.	Investigative	[55]
TP-801	DM4WTCE	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	1.08E-03	-0.24	-0.4
Lung cancer	2C82	Lung tissue	2.48E-02	-0.51	-0.69
Thyroid cancer	2C82	Thyroid	2.71E-34	1.52	2.67
Renal cancer	2C82	Kidney	2.88E-02	0.51	0.97
Head and neck cancer	2C82	Head and neck tissue	6.16E-01	0.31	0.37
Liver cancer	2C82	Liver tissue	9.24E-01	-0.08	-0.08

References

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