Drug Information

Drug (ID: DG01879) and It's Reported Resistant Information
Name
MEK inhibitors
Synonyms
MEK inhibitors
    Click to Show/Hide
Indication
In total 4 Indication(s)
Melanoma [ICD-11: 2C30]
Approved
[1]
Thyroid cancer [ICD-11: 2D10]
Phase 3
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1/2
[1]
Non-small-cell lung cancer [ICD-11: 2C25]
Phase 2
[1]
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Melanoma [ICD-11: 2C30]
[2]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Melanoma [ICD-11: 2C30]
[3]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[3]
Target MAPK/ERK kinase kinase (MAP3K) NOUNIPROTAC [1]
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
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
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1) [4]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.C121S (c.361T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 7B7R
Mutant Type Structure Method: X-ray diffraction Resolution: 2.01  Å
PDB: 7F2X
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.36
TM score: 0.87257
Amino acid change:
C121S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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20
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M
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A
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H
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H
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H
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H
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H
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H
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A
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A
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30
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A
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E
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N
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L
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40
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50
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60
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70
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80
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90
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100
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110
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120
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130
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140
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150
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160
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170
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180
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190
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200
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220
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230
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240
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250
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260
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300
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310
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330
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360
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Human melanoma tissue N.A.
Mechanism Description The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by unusual activation of pro-survival pathway
References
Ref 1 Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trialLancet Oncol. 2012 Aug;13(8):782-9. doi: 10.1016/S1470-2045(12)70269-3. Epub 2012 Jul 16.
Ref 2 The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014 Jan;4(1):94-109. doi: 10.1158/2159-8290.CD-13-0617. Epub 2013 Nov 21.
Ref 3 MEK1 mutations confer resistance to MEK and B-RAF inhibitionProc Natl Acad Sci U S A. 2009 Dec 1;106(48):20411-6. doi: 10.1073/pnas.0905833106. Epub 2009 Nov 13.
Ref 4 Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profilingJ Clin Oncol. 2011 Aug 1;29(22):3085-96. doi: 10.1200/JCO.2010.33.2312. Epub 2011 Mar 7.

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