Drug Information

Drug (ID: DG01892) and It's Reported Resistant Information
Name
MET inhibitors
Synonyms
MET inhibitors
    Click to Show/Hide
Indication
In total 5 Indication(s)
Squamous head and neck cell carcinom [ICD-11: 2D60]
Approved
[1]
Breast cancer [ICD-11: 2C60]
Phase 1
[1]
Renal cell carcinoma [ICD-11: 2C90]
Phase 1
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Gastric adenocarcinoma [ICD-11: 2B72]
Investigative
[1]
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[2]
Target Vascular endothelial growth factor receptor 2 (KDR) VGFR2_HUMAN [1]
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.H1112L (c.3335A>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) CVCL_0594
Gastric cancer [ICD-11: 2B72]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [3]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Molecule Alteration Copy number gain
.
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Liver cancer [ICD-11: 2C12]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [4]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
 Disease Info 
Molecule Alteration Copy number gain
.
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [2]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D1228V (c.3683A>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 5HNI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.67  Å
PDB: 6SDC
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.85
TM score: 0.88477
Amino acid change:
D1228V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
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1040
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1050
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A
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1060
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1070
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1080
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F
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1090
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G
G
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G
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L
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1100
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N
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G
K
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H
C
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A
A
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V
1110
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1120
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1130
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M
K
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1140
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L
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L
G
G
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C
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1150
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Y
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1160
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M
M
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H
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G
D
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R
N
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F
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1170
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N
E
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T
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H
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V
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K
1180
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L
L
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I
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G
F
F
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G
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V
A
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1190
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K
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G
M
M
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A
A
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1200
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F
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V
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R
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A
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1210
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M
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1220
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A
A
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F
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L
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M
1230
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Y
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E
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1240
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T
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G
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1250
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1260
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1270
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1280
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1290
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1300
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model PC9 cells Lung Homo sapiens (Human) CVCL_B260
293T cells Breast Homo sapiens (Human) CVCL_0063
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description There is a patient with metastatic NSCLC with MET-mediated resistance to EGFR TKI who responded to treatment with a type I MET inhibitor, savolitinib, given in combination with a third-generation EGFR inhibitor, osimertinib. The patient then developed acquired resistance mediated by a novel MET kinase domain mutation.
Kidney cancer [ICD-11: 2C90]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [5]
Sensitive Disease Renal cell carcinoma [ICD-11: 2C90.0]
 Disease Info 
Molecule Alteration Copy number gain
.
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Hepatocyte growth factor receptor (MET) [5]
Sensitive Disease Renal cell carcinoma [ICD-11: 2C90.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H1094R (c.3281A>G)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Renal cell carcinoma tissue N.A.
Mechanism Description The missense mutation p.H1094R (c.3281A>G) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target
Key Molecule: Hepatocyte growth factor receptor (MET) [6]
Sensitive Disease Renal cell carcinoma [ICD-11: 2C90.0]
 Disease Info 
Molecule Alteration Missense mutation
p.M1268T (c.3803T>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Human renal cell carcinoma tissue N.A.
Mechanism Description The missense mutation p.M1268T (c.3803T>C) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target
References
Ref 1 Abstract 1786: Characterization of the inhibitory capacity of EMD1214063, a novel small molecule inhibitor of the MET hepatocyte growth factor receptor on a panel of MET mutated variants.
Ref 2 Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer. Cancer Discov. 2016 Dec;6(12):1334-1341. doi: 10.1158/2159-8290.CD-16-0686. Epub 2016 Sep 30.
Ref 3 Indian J Med Paediatr Oncol. 2015 Apr-Jun;36(2):133-6. doi: 10.4103/0971-5851.158852.
Ref 4 STATISTICS/DATA TYPE - iGMDR.
Ref 5 Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinomaJ Clin Oncol. 2013 Jan 10;31(2):181-6. doi: 10.1200/JCO.2012.43.3383. Epub 2012 Dec 3.
Ref 6 Initial clinical sensitivity and acquired resistance to MET inhibition in MET-mutated papillary renal cell carcinomaJ Clin Oncol. 2013 Jun 1;31(16):e254-8. doi: 10.1200/JCO.2012.46.4289. Epub 2013 Apr 22.

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