Drug Information

Drug (ID: DG01507) and It's Reported Resistant Information
Name
Binimetinib
Synonyms
Binimetinib; 606143-89-9; MEK162; ARRY-162; ARRY-438162; MEK-162; Mektovi; 5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide; ARRY 162; Binimetinib (MEK-162); ARRY 438162; UNII-181R97MR71; MEK162 (ARRY-162, ARRY-438162); NVP-MEK162; MFCD22124525; Binimetinib (MEK162, ARRY-162, ARRY-438162); 181R97MR71; 6-(4-bromo-2-fluoroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide; 5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide.; 5-(4-Bromo-2-fluoroanilino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide; Binimetinib [USAN:INN]; binimetinibum; Mektovi (TN); ARRY-162; ARRY-438162; MEK 162; ARRY 162; ARRY 438162; Binimetinib; Mek162; Mek162, Binimetinib; MEK162(Binimetinib); Binimetinib (MEK162); Binimetinib (JAN/USAN); MLS006011180; C17H15BrF2N4O3; SCHEMBL570088; GTPL7921; CHEMBL3187723; MEK162 (Arry-162); AMY9056; AOB2072; DTXSID70209422; QCR-138; ARRY-162,MEK-162; CHEBI:145371; BDBM520649; HMS3652J14; HMS3747G09; BCP06780; EX-A1024; NSC764042; NSC788187; NSC799361; s7007; ZINC38460704; AKOS026750517; CCG-269133; CS-0627; DB11967; NSC-764042; NSC-788187; NSC-799361; SB16501; NCGC00345804-01; NCGC00345804-10; 1073666-70-2; 5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methylbenzimidazole-6-carboxamide; 6-(4-bromo-2-fluorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide; AC-29023; AS-16706; DA-35030; HY-15202; SMR004702949; SY284756; cas:606143-89-9;MEK162; FT-0697088; SW219910-1; Y1468; D10604; Binimetinib;MEK-162; ARRY-162;ARRY-438162; J-516581; Q19903515; US11147816, Binimetinib (ARRY-162, ARRY-438162); 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide; 5-[(4-Bromo-2-Fluorophenyl)Amino]-4-Fluoro-N-(2-Hydroxyethoxy)-1-Methyl-1H-Benzimidazole-6-Carboxami; 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide; 6-[(4-bromo-2-fluorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; N-(2-hydroxyethoxy)-4-fluoro-5-(2-fluoro-4-bromophenylamino)-1-methyl-1H-benzoimidazole-6-carboxamide; QO7
    Click to Show/Hide
Indication
In total 1 Indication(s)
Non-small-cell lung cancer [ICD-11: 2C25]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[2]
Target Epidermal growth factor receptor (EGFR) EGFR_HUMAN [3]
Erbb2 tyrosine kinase receptor (HER2) ERBB2_HUMAN [3]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
6
IsoSMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO
InChI
InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
InChIKey
ACWZRVQXLIRSDF-UHFFFAOYSA-N
PubChem CID
10288191
ChEBI ID
CHEBI:145371
TTD Drug ID
D05UFG
VARIDT ID
DR0214
INTEDE ID
DR01336
DrugBank ID
DB11967
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  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
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V211D (c.632T>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
Phoenix AMPHO cells Fetal kidney Homo sapiens (Human) CVCL_H716
In Vivo Model NOD scid gamma xenograft model Mus musculus
Experiment for
Molecule Alteration		 Single cell sequencing assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Hras (HRAS) [4]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.G12V (c.35G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 7SCW
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7SCX
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99104
Amino acid change:
G12V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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180
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T
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C
C
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M
M
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model T24 cells Bladder Homo sapiens (Human) CVCL_0554
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
RL952 cells Endometrium Homo sapiens (Human) CVCL_0505
NCI-H1915 cells Lung Homo sapiens (Human) CVCL_1505
KYSE-30 cells Esophagus Homo sapiens (Human) CVCL_1351
KNS62 cells Brain Homo sapiens (Human) CVCL_1335
HCC78 cells Pleural effusion Homo sapiens (Human) CVCL_2061
HCC44 cells Lung Homo sapiens (Human) CVCL_2060
CAL-12T cells Lung Homo sapiens (Human) CVCL_1105
In Vivo Model CB17 SCID-/- mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay
Key Molecule: GTPase Hras (HRAS) [4]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61R (c.182A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 7F68
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.46
TM score: 0.94384
Amino acid change:
Q61R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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E
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I
R
R
Q
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Y
Y
R
R
M
M
K
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170
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K
-
L
-
N
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model T24 cells Bladder Homo sapiens (Human) CVCL_0554
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
RL952 cells Endometrium Homo sapiens (Human) CVCL_0505
NCI-H1915 cells Lung Homo sapiens (Human) CVCL_1505
KYSE-30 cells Esophagus Homo sapiens (Human) CVCL_1351
KNS62 cells Brain Homo sapiens (Human) CVCL_1335
HCC78 cells Pleural effusion Homo sapiens (Human) CVCL_2061
HCC44 cells Lung Homo sapiens (Human) CVCL_2060
CAL-12T cells Lung Homo sapiens (Human) CVCL_1105
In Vivo Model CB17 SCID-/- mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61K (c.181C>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.74  Å
PDB: 8VM2
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.75
TM score: 0.98025
Amino acid change:
Q61K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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M
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N
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: GTPase Nras (NRAS) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61R (c.182A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 7F68
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.46
TM score: 0.94384
Amino acid change:
Q61R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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R
R
Q
Q
Y
Y
R
R
M
M
K
K
170
|
K
-
L
-
N
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: GTPase Nras (NRAS) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61R (c.182A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 7F68
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.46
TM score: 0.94384
Amino acid change:
Q61R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
G
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
R
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
S
S
K
K
S
D
90
|
F
F
A
A
D
D
I
I
N
N
L
L
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
D
D
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
T
T
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
H
H
E
E
L
L
A
A
K
K
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
E
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
Q
Q
Y
Y
R
R
M
M
K
K
170
|
K
-
L
-
N
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
420
|
M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
|
H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
|
T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
|
W
W
E
E
I
I
P
P
D
D
G
G
Q
Q
I
I
T
T
V
V
460
|
G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
|
T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
|
V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
|
P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
|
N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
|
H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
|
S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
|
Q
Q
W
W
C
C
E
E
G
G
S
S
S
S
L
L
Y
Y
H
H
540
|
H
H
L
L
H
H
I
I
I
I
E
E
T
T
K
K
F
F
E
E
550
|
M
M
I
I
K
K
L
L
I
I
D
D
I
I
A
A
R
R
Q
Q
560
|
T
T
A
A
Q
Q
G
G
M
M
D
D
Y
Y
L
L
H
H
A
A
570
|
K
K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
A
A
M
M
690
|
K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
K
K
K
K
700
|
K
K
R
R
D
D
E
E
R
R
P
P
L
L
F
F
P
P
Q
Q
710
|
I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
|
S
S
L
L
P
P
K
K
I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L597S (c.1789_1790delCTinsTC)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MAPK signaling pathway Inhibition hsa04010
In Vitro Model Skin sample N.A.
In Vivo Model Mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Crystal violet staining assay
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600X (c.1798_1800)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.V600X (c.1798_1800) in gene BRAF cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: GTPase Nras (NRAS) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61L (c.182A>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.Q61L (c.182A>T) in gene NRAS cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
Key Molecule: GTPase Nras (NRAS) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61L (c.182A>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Cutaneous melanoma tissue N.A.
Mechanism Description The missense mutation p.Q61L (c.182A>T) in gene NRAS cause the sensitivity of Binimetinib by unusual activation of pro-survival pathway
References
Ref 1 MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 studyLancet Oncol. 2013 Mar;14(3):249-56. doi: 10.1016/S1470-2045(13)70024-X. Epub 2013 Feb 13.
Ref 2 V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon CancerCancer Discov. 2019 Sep;9(9):1182-1191. doi: 10.1158/2159-8290.CD-19-0356. Epub 2019 Jun 21.
Ref 3 Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant MelanomasClin Cancer Res. 2018 Dec 15;24(24):6483-6494. doi: 10.1158/1078-0432.CCR-17-3384. Epub 2018 Jun 14.
Ref 4 Mutant HRAS as novel target for MEK and mTOR inhibitorsOncotarget. 2015 Dec 8;6(39):42183-96. doi: 10.18632/oncotarget.5619.

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