Drug Information

Drug (ID: DG01505) and It's Reported Resistant Information
Name
Selumetinib
Synonyms
Selumetinib; 606143-52-6; AZD6244; AZD 6244; ARRY-142886; 5-[(4-BROMO-2-CHLOROPHENYL)AMINO]-4-FLUORO-N-(2-HYDROXYETHOXY)-1-METHYL-1H-BENZIMIDAZOLE-6-CARBOXAMIDE; AZD-6244; Selumetinib (AZD6244); ARRY 142886; AZD6244 (Selumetinib); ARRY-886; UNII-6UH91I579U; 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide; 5-(4-broMo-2-chlorophenylaMino)-4-fluoro-N-(2-hydroxyethoxy)-1-Methyl-1H-benzo[d]iMidazole-6-carboxaMide; CHEMBL1614701; CHEBI:90227; 6UH91I579U; NCGC00189073-01; NCGC00189073-02; C17H15BrClFN4O3; 6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; DSSTox_CID_28870; DSSTox_RID_83139; DSSTox_GSID_48944; 1H-Benzimidazole-6-carboxamide, 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide; AZD 6244;5-((4-Bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidazole-6-carboxamide;6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide; CAS-606143-52-6; ARRY142886; Selumetinib [USAN:INN]; selumetinibum; Koselugo; 1H-Benzimidazole-6-carboxamide, 5-((4-bromo-2-chlorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-; 3EW; Selumetinib (USAN/INN); AZD6244 - Selumetinib; AZD 6244 (Selumetinib); SCHEMBL155456; GTPL5665; QCR-91; Selumetinib, ARRY-142886; DTXSID3048944; EX-A020; SYN1016; BCPP000367; HMS3244G03; HMS3244G04; HMS3244H03; HMS3265K01; HMS3265K02; HMS3265L01; HMS3265L02; HMS3654O03; NSC 741O78; AOB87732; BCP01739; Tox21_113362; BDBM50355497; MFCD11977472; NSC741078; NSC800882; s1008; ZINC31773258; AKOS015904255; Tox21_113362_1; BCP9000354; CCG-264774; CS-0059; DB11689; EX-8621; NSC-741078; NSC-800882; SB14707; NCGC00189073-07; AC-25059; AM808016; AZD6244,Selumetinib, ARRY-142886; BC004624; HY-50706; Selumetinib (ARRY142886/AZD6244); AZD6244 (Selumetinib,ARRY-142886); FT-0674552; SW202561-3; X2640; D09666; 143A526; Q-101405; Q7448840; BRD-K57080016-001-01-9; 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy -ethoxy)-amide; 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxy-ethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide; 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid(2-hydroxyethoxy)-amide; 6-(4-bromo-2chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide
    Click to Show/Hide
Indication
In total 2 Indication(s)
Parkinson disease [ICD-11: 8A00]
Phase 3
[1]
Parkinson disease [ICD-11: 8A00]
Phase 3
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Acute myeloid leukemia [ICD-11: 2A60]
[2]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (6 diseases)
Colorectal cancer [ICD-11: 2B91]
[3]
Bladder cancer [ICD-11: 2C94]
[5]
Endometrial cancer [ICD-11: 2C76]
[6]
Lung cancer [ICD-11: 2C25]
[7]
Melanoma [ICD-11: 2C30]
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[8]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
Esophageal cancer [ICD-11: 2B70]
[4]
Target 5-HT 2A receptor (HTR2A) 5HT2A_HUMAN [9]
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)Cl)C(=O)NOCCO
InChI
InChI=1S/C17H15BrClFN4O3/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
CYOHGALHFOKKQC-UHFFFAOYSA-N
PubChem CID
10127622
ChEBI ID
CHEBI:90227
TTD Drug ID
D0J8JP
DrugBank ID
DB11689
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  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
Brain cancer [ICD-11: 2A00]
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: Serine/threonine-protein kinase B-raf (BRAF) [9]
Sensitive Disease FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
 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
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [9]
Sensitive Disease FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
 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
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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) [8]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V211D (c.632T>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of Selumetinib by unusual activation of pro-survival pathway
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 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
-
20
|
M
-
A
-
H
-
H
-
H
-
H
-
H
-
H
-
A
-
A
-
30
|
A
-
E
-
N
-
L
-
Y
-
F
-
Q
-
L
-
E
-
E
-
40
|
L
-
E
-
L
M
D
T
E
L
Q
Q
Q
Q
R
R
K
K
R
R
50
|
L
L
E
E
A
A
F
F
L
L
T
T
Q
Q
K
K
Q
Q
K
K
60
|
V
V
G
G
E
E
L
L
K
K
D
D
D
D
D
D
F
F
E
E
70
|
K
K
I
I
S
S
E
E
L
L
G
G
A
A
G
G
N
N
G
G
80
|
G
G
V
V
V
V
F
F
K
K
V
V
S
S
H
H
K
K
P
P
90
|
S
S
G
G
L
L
V
V
M
M
A
A
R
R
K
K
L
L
I
I
100
|
H
H
L
L
E
E
I
I
K
K
P
P
A
A
I
I
R
R
N
N
110
|
Q
Q
I
I
I
I
R
R
E
E
L
L
Q
Q
V
V
L
L
H
H
120
|
E
E
C
S
N
N
S
S
P
P
Y
Y
I
I
V
V
G
G
F
F
130
|
Y
Y
G
G
A
A
F
F
Y
Y
S
S
D
D
G
G
E
E
I
I
140
|
S
S
I
I
C
C
M
M
E
E
H
H
M
M
D
D
G
G
G
G
150
|
S
S
L
L
D
D
Q
Q
V
V
L
L
K
K
K
K
A
A
G
G
160
|
R
R
I
I
P
P
E
E
Q
Q
I
I
L
L
G
G
K
K
V
V
170
|
S
S
I
I
A
A
V
V
I
I
K
K
G
G
L
L
T
T
Y
Y
180
|
L
L
R
R
E
E
K
K
H
H
K
K
I
I
M
M
H
H
R
R
190
|
D
D
V
V
K
K
P
P
S
S
N
N
I
I
L
L
V
V
N
N
200
|
S
S
R
R
G
G
E
E
I
I
K
K
L
L
C
C
D
D
F
F
210
|
G
G
V
V
S
S
G
G
Q
Q
L
L
I
I
D
D
S
S
M
M
220
|
A
A
N
N
S
S
F
F
V
V
G
G
T
T
R
R
S
S
Y
Y
230
|
M
M
S
S
P
P
E
E
R
R
L
L
Q
Q
G
G
T
T
H
H
240
|
Y
Y
S
S
V
V
Q
Q
S
S
D
D
I
I
W
W
S
S
M
M
250
|
G
G
L
L
S
S
L
L
V
V
E
E
M
M
A
A
V
V
G
G
260
|
R
R
Y
Y
P
P
I
I
-
G
-
S
-
G
-
S
-
G
-
S
270
|
-
M
-
A
-
I
-
F
-
E
-
L
-
L
-
D
-
Y
-
I
280
|
-
V
-
N
-
E
-
P
-
P
-
P
-
K
-
L
-
P
-
S
290
|
-
G
-
V
-
F
-
S
-
L
-
E
-
F
-
Q
-
D
-
F
300
|
-
V
-
N
G
K
S
C
G
L
S
I
G
K
S
N
M
P
A
A
310
|
I
E
F
R
E
A
L
D
L
L
D
K
Y
Q
I
L
V
M
N
V
320
|
E
H
P
A
P
F
P
I
K
K
L
R
P
S
S
D
G
A
V
E
330
|
F
E
S
V
L
D
E
F
F
A
Q
G
D
W
F
L
V
C
N
S
340
|
K
T
C
I
L
G
I
L
K
N
N
Q
P
P
A
S
E
T
R
P
350
|
A
T
D
H
L
A
K
A
Q
G
L
E
M
G
V
H
H
H
A
H
360
|
F
H
I
H
K
H
R
-
S
-
D
-
A
-
E
-
E
-
V
-
370
|
D
-
F
-
A
-
G
-
W
-
L
-
C
-
S
-
T
-
I
-
380
|
G
-
L
-
N
-
Q
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.F53L (c.157T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Q56P (c.167A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K57N (c.171G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.I111S (c.332T>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [8]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.F129L (c.385T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Acute myeloid leukemia [ICD-11: 2A60]
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: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [2]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Molecule Alteration IF-deletion
p.Q569_G613 (c.1705_1837)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Blood N.A.
Experiment for
Molecule Alteration		 Gentra puregene assay
Experiment for
Drug Resistance		 p-ERK1/2 and p-mTOR analysis
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Molecule Alteration Synonymous
p.L862L (c.2586G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Blood N.A.
Experiment for
Molecule Alteration		 Gentra puregene assay
Experiment for
Drug Resistance		 p-ERK1/2 and p-mTOR analysis
Esophageal cancer [ICD-11: 2B70]
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: Histone H1.4 (H1-4) [4]
Resistant Disease Oesophagus adenocarcinoma [ICD-11: 2B70.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
In Vivo Model Patient-derived esophageal cancer model Homo sapiens
Experiment for
Molecule Alteration		 Gene expression analysis
Experiment for
Drug Resistance		 Drug sensitivity analysis
Mechanism Description The results of drug sensitivity of risk genes showed that the high expression of HIST1H1E made tumor cells resistant to trametinib, selumetinib, RDEA119, Docetaxel and 17-AAG. The high expression of UBE2C makes tumor cells resistant to masitinib. The low expression of ERO1B makes the EC more sensitive to FK866
Gastric cancer [ICD-11: 2B72]
Click to Show/Hide
Drug Sensitivity 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) [10]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q56P (c.167A>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
OCUM-1 cells Pleural effusion Homo sapiens (Human) CVCL_3084
NUGC-4 cells Lymph node Homo sapiens (Human) CVCL_3082/CVCL_8372
Experiment for
Molecule Alteration		 Multiplex deep sequencing of MAP2K1 cDNAs assay
Experiment for
Drug Resistance		 Focus formation assay
Mechanism Description The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target
Colorectal cancer [ICD-11: 2B91]
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: AKT serine/threonine kinase (AKT) [3]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Phosphorylation
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-Akt signaling pathway Activation hsa04151
In Vitro Model BRAF L525R cells N.A. Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description The MEK inhibitor selumetinib effectively inhibited cell proliferation and ERK phosphorylation in?BRAF?L525R cells but not in?BRAF?V600E cells. Further studies revealed that AKT phosphorylation was reduced by selumetinib in?BRAF?L525R cells but not in?BRAF?V600E cells or selumetinib-resistant?BRAF?L525R cells. Moreover, the AKT inhibitor overcame the selumetinib resistance.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Integrin alpha-2 (ITGA2) [11]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT8 cells Colon Homo sapiens (Human) CVCL_2478
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
In Vivo Model BALB/c nude mice model Mus musculus
Experiment for
Molecule Alteration		 Western blot assay; qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Apoptosis assay; Clone formation assay; Immunohistochemistry
Mechanism Description ACOX1 and ITGA2 were identified as risk biomarkers associated with 5-FU-resistance. We developed a risk signature, consisting of ACOX1 and ITGA2, that was able to distinguish well between 5-FU-resistance and 5-FU-sensitive. The single-cell sequencing data showed that ITGA2 was mainly enriched in malignant cells. ITGA2 was negatively correlated with IC50 values of most small molecule inhibitors, of which selumetinib had the highest negative correlation. Finally, knocking down ITGA2 can make 5-FU-resistant CRC cells sensitive to 5-FU and combining with selumetinib can improve the therapeutic effect of 5-FU resistant cells.
Lung cancer [ICD-11: 2C25]
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: Epidermal growth factor receptor (EGFR) [7]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T790M (c.2369C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.10  Å
PDB: 2J6M
Mutant Type Structure Method: X-ray diffraction Resolution: 3.05  Å
PDB: 2JIU
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.57
TM score: 0.92063
Amino acid change:
T790M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
S
G
G
E
E
A
A
P
P
700
|
N
N
Q
Q
A
A
L
L
L
L
R
R
I
I
L
L
K
K
E
E
710
|
T
T
E
E
F
F
K
K
K
K
I
I
K
K
V
V
L
L
G
G
720
|
S
S
G
G
A
A
F
F
G
G
T
T
V
V
Y
Y
K
K
G
G
730
|
L
L
W
W
I
I
P
P
E
E
G
G
E
E
K
K
V
V
K
K
740
|
I
I
P
P
V
V
A
A
I
I
K
K
E
E
L
L
R
R
E
E
750
|
A
A
T
T
S
S
P
P
K
K
A
A
N
N
K
K
E
E
I
I
760
|
L
L
D
D
E
E
A
A
Y
Y
V
V
M
M
A
A
S
S
V
V
770
|
D
D
N
N
P
P
H
H
V
V
C
C
R
R
L
L
L
L
G
G
780
|
I
I
C
C
L
L
T
T
S
S
T
T
V
V
Q
Q
L
L
I
I
790
|
T
M
Q
Q
L
L
M
M
P
P
F
F
G
G
C
C
L
L
L
L
800
|
D
D
Y
Y
V
V
R
R
E
E
H
H
K
K
D
D
N
N
I
I
810
|
G
G
S
S
Q
Q
Y
Y
L
L
L
L
N
N
W
W
C
C
V
V
820
|
Q
Q
I
I
A
A
K
K
G
G
M
M
N
N
Y
Y
L
L
E
E
830
|
D
D
R
R
R
R
L
L
V
V
H
H
R
R
D
D
L
L
A
A
840
|
A
A
R
R
N
N
V
V
L
L
V
V
K
K
T
T
P
P
Q
Q
850
|
H
H
V
V
K
K
I
I
T
T
D
D
F
F
G
G
L
L
A
A
860
|
K
K
L
L
L
L
G
G
A
A
E
E
E
E
K
K
E
E
Y
Y
870
|
H
H
A
A
E
E
G
G
G
G
K
K
V
V
P
P
I
I
K
K
880
|
W
W
M
M
A
A
L
L
E
E
S
S
I
I
L
L
H
H
R
R
890
|
I
I
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
900
|
Y
Y
G
G
V
V
T
T
V
V
W
W
E
E
L
L
M
M
T
T
910
|
F
F
G
G
S
S
K
K
P
P
Y
Y
D
D
G
G
I
I
P
P
920
|
A
A
S
S
E
E
I
I
S
S
S
S
I
I
L
L
E
E
K
K
930
|
G
G
E
E
R
R
L
L
P
P
Q
Q
P
P
P
P
I
I
C
C
940
|
T
T
I
I
D
D
V
V
Y
Y
M
M
I
I
M
M
V
V
K
K
950
|
C
C
W
W
M
M
I
I
D
D
A
A
D
D
S
S
R
R
P
P
960
|
K
K
F
F
R
R
E
E
L
L
I
I
I
I
E
E
F
F
S
S
970
|
K
K
M
M
A
A
R
R
D
D
P
P
Q
Q
R
R
Y
Y
L
L
980
|
V
V
I
I
Q
Q
G
G
D
D
E
E
R
R
M
M
H
H
L
L
990
|
P
P
S
S
P
P
T
T
D
D
S
S
N
N
F
F
Y
Y
R
R
1000
|
A
A
L
L
M
M
D
D
E
E
E
E
D
D
M
M
D
D
D
D
1010
|
V
V
V
V
D
D
A
A
D
D
E
E
Y
Y
L
L
I
I
P
P
1020
|
Q
Q
Q
Q
G
G
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCI-H1975 cells Lung Homo sapiens (Human) CVCL_1511
In Vivo Model BALB/C nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Immunohistochemistry assay
Experiment for
Drug Resistance		 MTT assay
Drug Sensitivity 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) [12]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q56P (c.167A>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
AGS cells Gastric Homo sapiens (Human) CVCL_0139
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
SW48 cells Colon Homo sapiens (Human) CVCL_1724
A549 cells Lung Homo sapiens (Human) CVCL_0023
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
NCI-H1650 cells Lung Homo sapiens (Human) CVCL_1483
SW1573 cells Lung Homo sapiens (Human) CVCL_1720
SNU-C1 cells Peritoneum Homo sapiens (Human) CVCL_1708
OCUM-1 cells Pleural effusion Homo sapiens (Human) CVCL_3084
NCI-H226 cells Pleural effusion Homo sapiens (Human) CVCL_1544
NCI-H196 cells Pleural effusion Homo sapiens (Human) CVCL_1509
NCI-H1437 cells Pleural effusion Homo sapiens (Human) CVCL_1472
NCI-H1355 cells Pleural effusion Homo sapiens (Human) CVCL_1464
MKN7 cells Lymph node Homo sapiens (Human) CVCL_1417
NCI-H1299 cells Lymph node Homo sapiens (Human) CVCL_0060
HCC366 cells Lung Homo sapiens (Human) CVCL_2059
NCI-H2126 cells Pleural effusion Homo sapiens (Human) CVCL_1532
In Vivo Model Female nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [13]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 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
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-10
|
-
S
-
S
-
G
-
R
-
E
-
N
-
L
-
Y
-
F
-
Q
0
|
S
G
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
K
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
S
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
K
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
SW1271 cells Lung Homo sapiens (Human) CVCL_1716
H2347 cells Lung Homo sapiens (Human) CVCL_1550
H2087 cells Lymph node Homo sapiens (Human) CVCL_1524
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell Titer blue reagent assay
Mechanism Description The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [14]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K57N (c.171G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Trypan blue staining assay
Mechanism Description The missense mutation p.K57N (c.171G>T) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: MAPK/ERK kinase 1 (MEK1) [14]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.K57N (c.171G>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Trypan blue staining assay
Mechanism Description The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Melanoma [ICD-11: 2C30]
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) [15]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q56P (c.167A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target
Key Molecule: MAPK/ERK kinase 1 (MEK1) [15]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I103N (c.308T>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target
Key Molecule: MAPK/ERK kinase 1 (MEK1) [15]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L115P (c.344T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target
Key Molecule: MAPK/ERK kinase 1 (MEK1) [15]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.P124S (c.370C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description The missense mutation p.P124S (c.370C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target
Key Molecule: MAPK/ERK kinase 1 (MEK1) [15]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.P124L (c.371C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
293T cells Breast Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description The missense mutation p.P124L (c.371C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61L (c.182A>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
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
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-10
|
-
S
-
S
-
G
-
R
-
E
-
N
-
L
-
Y
-
F
-
Q
0
|
S
G
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
K
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
S
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
K
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
Key Molecule: GTPase Nras (NRAS) [16]
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
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-10
|
-
S
-
S
-
G
-
R
-
E
-
N
-
L
-
Y
-
F
-
Q
0
|
S
G
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
K
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
S
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
K
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Skin N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.Q61K (c.181C>A) in gene NRAS cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target
Key Molecule: GTPase Nras (NRAS) [17]
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
Experiment for
Drug Resistance		 MTD assay
Mechanism Description The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of Selumetinib 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.G13D (c.38G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.01  Å
PDB: 6P0Z
Mutant Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 8BLR
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.48
TM score: 0.8385
Amino acid change:
G13D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
G
-
G
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
G
G
D
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
Q
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
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
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
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
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
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [18]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [18]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [18]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: Guanine nucleotide-binding protein subunit alpha-11 (GNA11) [18]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Key Molecule: GTPase Nras (NRAS) [17]
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
Experiment for
Drug Resistance		 MTD assay
Mechanism Description The missense mutation p.Q61L (c.182A>T) in gene NRAS cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: Cellular tumor antigen p53 (TP53) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.D259Y (c.775G>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
Breast cancer [ICD-11: 2C60]
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: Insulin-like growth factor 1 receptor (IGF1R) [19]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Cell cycle assay; Tissue microarrays staining assay
Mechanism Description MEK (mitogen-activated protein kinase kinase)1/2 inhibitors, including PD0325901, selumetinib, trametinib and TAK-733, selectively antagonized IGF1R signaling-mediated antiestrogen resistance but did not affect cell proliferation under normal growth conditions. RNAseq analysis revealed that MEK inhibitors PD0325901 and selumetinib drastically altered cell cycle progression and cell migration networks under IGF1R signaling-mediated antiestrogen resistance.
Ovarian cancer [ICD-11: 2C73]
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: MAPK/ERK kinase 1 (MEK1) [20]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Molecule Alteration IF-deletion
p.Q56_V60delQKQKV (c.166_180del15)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ovary N.A.
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Whole transcriptome analysis
Experiment for
Drug Resistance		 Colony formation assay
Endometrial cancer [ICD-11: 2C76]
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: Fibroblast growth factor receptor 2 (FGFR2) [6]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Bladder cancer [ICD-11: 2C94]
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: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [5]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.09  Å
PDB: 3WLW
Mutant Type Structure Method: Electron microscopy Resolution: 3.09  Å
PDB: 7MN6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.33
TM score: 0.96205
Amino acid change:
S310F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
T
M
Q
E
V
L
C
A
T
A
G
L
T
C
D
R
M
W
10
|
K
G
L
L
R
L
L
L
P
A
A
L
S
L
P
P
E
P
T
G
20
|
H
A
L
A
D
S
M
T
L
Q
R
V
H
C
L
T
Y
G
Q
T
30
|
G
D
C
M
Q
K
V
L
V
R
Q
L
G
P
N
A
L
S
E
P
40
|
L
E
T
T
Y
H
L
L
P
D
T
M
N
L
A
R
S
H
L
L
50
|
S
Y
F
Q
L
G
Q
C
D
Q
I
V
Q
V
E
Q
V
G
Q
N
60
|
G
L
Y
E
V
L
L
T
I
Y
A
L
H
P
N
T
Q
N
V
A
70
|
R
S
Q
L
V
S
P
F
L
L
Q
Q
R
D
L
I
R
Q
I
E
80
|
V
V
R
Q
G
G
T
Y
Q
V
L
L
F
I
E
A
D
H
N
N
90
|
Y
Q
A
V
L
R
A
Q
V
V
L
P
D
L
N
Q
G
R
D
L
100
|
P
R
L
I
N
V
N
R
T
G
T
T
P
Q
V
L
T
F
G
E
110
|
A
D
S
N
P
Y
G
A
G
L
L
A
R
V
E
L
L
D
Q
N
120
|
L
G
R
D
S
P
L
L
T
N
E
N
I
T
L
T
K
P
G
V
130
|
G
T
V
G
L
A
I
S
Q
P
R
G
N
G
P
L
Q
R
L
E
140
|
C
L
Y
Q
Q
L
D
R
T
S
I
L
L
T
W
E
K
I
D
L
150
|
I
K
F
G
H
G
K
V
N
L
N
I
Q
Q
L
R
A
N
L
P
160
|
T
Q
L
L
I
C
D
Y
T
Q
N
D
R
T
S
I
R
L
A
W
170
|
C
K
H
D
P
I
C
F
S
H
P
K
M
N
C
N
K
Q
G
L
180
|
S
A
R
L
C
T
W
L
G
I
E
D
S
T
S
N
E
R
D
S
190
|
C
R
Q
A
S
C
L
H
T
P
R
C
T
S
V
P
C
M
A
C
200
|
G
K
G
G
C
S
A
R
R
C
C
W
K
G
G
E
P
S
L
S
210
|
P
E
T
D
D
C
C
Q
C
S
H
L
E
T
Q
R
C
T
A
V
220
|
A
C
G
A
C
G
T
G
G
C
P
A
K
R
H
C
S
K
D
G
230
|
C
P
L
L
A
P
C
T
L
D
H
C
F
C
N
H
H
E
S
Q
240
|
G
C
I
A
C
A
E
G
L
C
H
T
C
G
P
P
A
K
L
H
250
|
V
S
T
D
Y
C
N
L
T
A
D
C
T
L
F
H
E
F
S
N
260
|
M
H
P
S
N
G
P
I
E
C
G
E
R
L
Y
H
T
C
F
P
270
|
G
A
A
L
S
V
C
T
V
Y
T
N
A
T
C
D
P
T
Y
F
280
|
N
E
Y
S
L
M
S
P
T
N
D
P
V
E
G
G
S
R
C
Y
290
|
T
T
L
F
V
G
C
A
P
S
L
C
H
V
N
T
Q
A
E
C
300
|
V
P
T
Y
A
N
E
Y
D
L
G
S
T
T
Q
D
R
V
C
G
310
|
E
F
K
C
C
T
S
L
K
V
P
C
C
P
A
L
R
H
V
N
320
|
C
Q
Y
E
G
V
L
T
G
A
M
E
E
D
H
G
L
T
R
Q
330
|
E
R
V
C
R
E
A
K
V
C
T
S
S
K
A
P
N
C
I
A
340
|
Q
R
E
V
F
C
A
Y
G
G
C
L
K
G
K
M
I
E
F
H
350
|
G
L
S
R
L
E
A
V
F
R
L
A
P
V
E
T
S
S
F
A
360
|
D
N
G
I
D
Q
P
E
A
F
S
A
N
G
T
C
A
K
P
K
370
|
L
I
Q
F
P
G
E
S
Q
L
L
A
Q
F
V
L
F
P
E
E
380
|
T
S
L
F
E
D
E
G
I
D
T
P
G
A
Y
S
L
N
Y
T
390
|
I
A
S
P
A
L
W
Q
P
P
D
E
S
Q
L
L
P
Q
D
V
400
|
L
F
S
E
V
T
F
L
Q
E
N
E
L
I
Q
T
V
G
I
Y
410
|
R
L
G
Y
R
I
I
S
L
A
H
W
N
P
G
D
A
S
Y
L
420
|
S
P
L
D
T
L
L
S
Q
V
G
F
L
Q
G
N
I
L
S
Q
430
|
W
V
L
I
G
R
L
G
R
R
S
I
L
L
R
H
E
N
L
G
440
|
G
A
S
Y
G
S
L
L
A
T
L
L
I
Q
H
G
H
L
N
G
450
|
T
I
H
S
L
W
C
L
F
G
V
L
H
R
T
S
V
L
P
R
460
|
W
E
D
L
Q
G
L
S
F
G
R
L
N
A
P
L
H
I
Q
H
470
|
A
H
L
N
L
T
H
H
T
L
A
C
N
F
R
V
P
H
E
T
480
|
D
V
E
P
C
W
V
D
G
Q
E
L
G
F
L
R
A
N
C
P
490
|
H
H
Q
Q
L
A
C
L
A
L
R
H
G
T
H
A
C
N
W
R
500
|
G
P
P
E
G
D
P
E
T
C
Q
V
C
G
V
E
N
G
C
L
510
|
S
A
Q
C
F
H
L
Q
R
L
G
C
Q
A
E
R
C
G
V
H
520
|
E
C
E
W
C
G
R
P
V
G
L
P
Q
T
G
Q
L
C
P
V
530
|
R
N
E
C
Y
S
V
Q
N
F
A
L
R
R
H
G
C
Q
L
E
540
|
P
C
C
V
H
E
P
E
E
C
C
R
Q
V
P
L
Q
Q
N
G
550
|
G
L
S
P
V
R
T
E
C
Y
F
V
G
N
P
A
E
R
A
H
560
|
D
C
Q
L
C
P
V
C
A
H
-
P
-
E
-
C
-
Q
-
P
570
|
-
Q
-
N
-
G
-
S
-
V
-
T
-
C
-
F
-
G
-
P
580
|
-
E
-
A
-
D
-
Q
-
C
-
V
-
A
-
C
-
A
-
H
590
|
-
Y
-
K
-
D
-
P
-
P
-
F
-
C
-
V
-
A
-
R
600
|
-
C
-
P
-
S
-
G
-
V
-
K
-
P
-
D
-
L
-
S
610
|
-
Y
-
M
-
P
-
I
-
W
-
K
-
F
-
P
-
D
-
E
620
|
-
E
-
G
-
A
-
C
-
Q
-
P
-
C
-
P
-
I
-
N
630
|
-
C
-
T
-
H
-
S
-
C
-
V
-
D
-
L
-
D
-
D
640
|
-
K
-
G
-
C
-
P
-
A
-
E
-
Q
-
R
-
A
-
S
650
|
-
P
-
L
-
T
-
S
-
I
-
I
-
S
-
A
-
V
-
V
660
|
-
G
-
I
-
L
-
L
-
V
-
V
-
V
-
L
-
G
-
V
670
|
-
V
-
F
-
G
-
I
-
L
-
I
-
K
-
R
-
R
-
Q
680
|
-
Q
-
K
-
I
-
R
-
K
-
Y
-
T
-
M
-
R
-
R
690
|
-
L
-
L
-
Q
-
E
-
T
-
E
-
L
-
V
-
E
-
P
700
|
-
L
-
T
-
P
-
S
-
G
-
A
-
M
-
P
-
N
-
Q
710
|
-
A
-
Q
-
M
-
R
-
I
-
L
-
K
-
E
-
T
-
E
720
|
-
L
-
R
-
K
-
V
-
K
-
V
-
L
-
G
-
S
-
G
730
|
-
A
-
F
-
G
-
T
-
V
-
Y
-
K
-
G
-
I
-
W
740
|
-
I
-
P
-
D
-
G
-
E
-
N
-
V
-
K
-
I
-
P
750
|
-
V
-
A
-
I
-
K
-
V
-
L
-
R
-
E
-
N
-
T
760
|
-
S
-
P
-
K
-
A
-
N
-
K
-
E
-
I
-
L
-
D
770
|
-
E
-
A
-
Y
-
V
-
M
-
A
-
G
-
V
-
D
-
S
780
|
-
P
-
Y
-
V
-
S
-
R
-
L
-
L
-
G
-
I
-
C
790
|
-
L
-
T
-
S
-
T
-
V
-
Q
-
L
-
V
-
T
-
Q
800
|
-
L
-
M
-
P
-
Y
-
G
-
C
-
L
-
L
-
D
-
H
810
|
-
V
-
R
-
E
-
N
-
R
-
G
-
R
-
L
-
G
-
S
820
|
-
Q
-
D
-
L
-
L
-
N
-
W
-
C
-
M
-
Q
-
I
830
|
-
A
-
K
-
G
-
M
-
S
-
Y
-
L
-
E
-
D
-
V
840
|
-
R
-
L
-
V
-
H
-
R
-
D
-
L
-
A
-
A
-
R
850
|
-
N
-
V
-
L
-
V
-
K
-
S
-
P
-
N
-
H
-
V
860
|
-
K
-
I
-
T
-
D
-
F
-
G
-
L
-
A
-
R
-
L
870
|
-
L
-
D
-
I
-
D
-
E
-
T
-
E
-
Y
-
H
-
A
880
|
-
D
-
G
-
G
-
K
-
V
-
P
-
I
-
K
-
W
-
M
890
|
-
A
-
L
-
E
-
S
-
I
-
L
-
R
-
R
-
R
-
F
900
|
-
T
-
H
-
Q
-
S
-
D
-
V
-
W
-
S
-
Y
-
G
910
|
-
V
-
T
-
V
-
W
-
E
-
L
-
M
-
T
-
F
-
G
920
|
-
A
-
K
-
P
-
Y
-
D
-
G
-
I
-
P
-
A
-
R
930
|
-
E
-
I
-
P
-
D
-
L
-
L
-
E
-
K
-
G
-
E
940
|
-
R
-
L
-
P
-
Q
-
P
-
P
-
I
-
C
-
T
-
I
950
|
-
D
-
V
-
Y
-
M
-
I
-
M
-
V
-
K
-
C
-
W
960
|
-
M
-
I
-
D
-
S
-
E
-
C
-
R
-
P
-
R
-
F
970
|
-
R
-
E
-
L
-
V
-
S
-
E
-
F
-
S
-
R
-
M
980
|
-
A
-
R
-
D
-
P
-
Q
-
R
-
F
-
V
-
V
-
I
990
|
-
Q
-
N
-
E
-
D
-
L
-
G
-
P
-
A
-
S
-
P
1000
|
-
L
-
D
-
S
-
T
-
F
-
Y
-
R
-
S
-
L
-
L
1010
|
-
E
-
D
-
D
-
D
-
M
-
G
-
D
-
L
-
V
-
D
1020
|
-
A
-
E
-
E
-
Y
-
L
-
V
-
P
-
Q
-
Q
-
G
1030
|
-
G
-
G
-
S
-
L
-
E
-
V
-
L
-
F
-
Q
-
G
1040
|
-
P
-
S
-
S
-
P
-
S
-
G
-
S
-
S
-
M
-
K
1050
|
-
I
-
E
-
E
-
G
-
K
-
L
-
V
-
I
-
W
-
I
1060
|
-
N
-
G
-
D
-
K
-
G
-
Y
-
N
-
G
-
L
-
A
1070
|
-
E
-
V
-
G
-
K
-
K
-
F
-
E
-
K
-
D
-
T
1080
|
-
G
-
I
-
K
-
V
-
T
-
V
-
E
-
H
-
P
-
D
1090
|
-
K
-
L
-
E
-
E
-
K
-
F
-
P
-
Q
-
V
-
A
1100
|
-
A
-
T
-
G
-
D
-
G
-
P
-
D
-
I
-
I
-
F
1110
|
-
W
-
A
-
H
-
D
-
R
-
F
-
G
-
G
-
Y
-
A
1120
|
-
Q
-
S
-
G
-
L
-
L
-
A
-
E
-
I
-
T
-
P
1130
|
-
D
-
K
-
A
-
F
-
Q
-
D
-
K
-
L
-
Y
-
P
1140
|
-
F
-
T
-
W
-
D
-
A
-
V
-
R
-
Y
-
N
-
G
1150
|
-
K
-
L
-
I
-
A
-
Y
-
P
-
I
-
A
-
V
-
E
1160
|
-
A
-
L
-
S
-
L
-
I
-
Y
-
N
-
K
-
D
-
L
1170
|
-
L
-
P
-
N
-
P
-
P
-
K
-
T
-
W
-
E
-
E
1180
|
-
I
-
P
-
A
-
L
-
D
-
K
-
E
-
L
-
K
-
A
1190
|
-
K
-
G
-
K
-
S
-
A
-
L
-
M
-
F
-
N
-
L
1200
|
-
Q
-
E
-
P
-
Y
-
F
-
T
-
W
-
P
-
L
-
I
1210
|
-
A
-
A
-
D
-
G
-
G
-
Y
-
A
-
F
-
K
-
Y
1220
|
-
E
-
N
-
G
-
K
-
Y
-
D
-
I
-
K
-
D
-
V
1230
|
-
G
-
V
-
D
-
N
-
A
-
G
-
A
-
K
-
A
-
G
1240
|
-
L
-
T
-
F
-
L
-
V
-
D
-
L
-
I
-
K
-
N
1250
|
-
K
-
H
-
M
-
N
-
A
-
D
-
T
-
D
-
Y
-
S
1260
|
-
I
-
A
-
E
-
A
-
A
-
F
-
N
-
K
-
G
-
E
1270
|
-
T
-
A
-
M
-
T
-
I
-
N
-
G
-
P
-
W
-
A
1280
|
-
W
-
S
-
N
-
I
-
D
-
T
-
S
-
K
-
V
-
N
1290
|
-
Y
-
G
-
V
-
T
-
V
-
L
-
P
-
T
-
F
-
K
1300
|
-
G
-
Q
-
P
-
S
-
K
-
P
-
F
-
V
-
G
-
V
1310
|
-
L
-
S
-
A
-
G
-
I
-
N
-
A
-
A
-
S
-
P
1320
|
-
N
-
K
-
E
-
L
-
A
-
K
-
E
-
F
-
L
-
E
1330
|
-
N
-
Y
-
L
-
L
-
T
-
D
-
E
-
G
-
L
-
E
1340
|
-
A
-
V
-
N
-
K
-
D
-
K
-
P
-
L
-
G
-
A
1350
|
-
V
-
A
-
L
-
K
-
S
-
Y
-
E
-
E
-
E
-
L
1360
|
-
A
-
K
-
D
-
P
-
R
-
I
-
A
-
A
-
T
-
M
1370
|
-
E
-
N
-
A
-
Q
-
K
-
G
-
E
-
I
-
M
-
P
1380
|
-
N
-
I
-
P
-
Q
-
M
-
S
-
A
-
F
-
W
-
Y
1390
|
-
A
-
V
-
R
-
T
-
A
-
V
-
I
-
N
-
A
-
A
1400
|
-
S
-
G
-
R
-
Q
-
T
-
V
-
D
-
E
-
A
-
L
1410
|
-
K
-
D
-
A
-
Q
-
T
-
N
-
S
-
S
-
S
-
S
1420
|
-
G
-
P
-
S
-
S
-
P
-
S
-
A
-
W
-
S
-
H
1430
|
-
P
-
Q
-
F
-
E
-
K
-
G
-
G
-
G
-
S
-
G
1440
|
-
G
-
G
-
S
-
G
-
G
-
S
-
S
-
A
-
W
-
S
1450
|
-
H
-
P
-
Q
-
F
-
E
-
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [5]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S653C (c.1958C>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Uveal melanoma [ICD-11: 2D0Y]
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: Guanine nucleotide-binding protein alpha-q (GNAQ) [21]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Omm13 cells N.A. N.A. N.A.
Mel270 cells Skin Homo sapiens (Human) CVCL_C302
Mel202 cells Eye Homo sapiens (Human) CVCL_C301
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description The missense mutation p.Q209L (c.626A>T) in gene GNAQ cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [21]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209P (c.626A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Omm13 cells N.A. N.A. N.A.
Mel270 cells Skin Homo sapiens (Human) CVCL_C302
Mel202 cells Eye Homo sapiens (Human) CVCL_C301
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description The missense mutation p.Q209P (c.626A>C) in gene GNAQ cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway
Thyroid cancer [ICD-11: 2D10]
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: Serine/threonine-protein kinase B-raf (BRAF) [22]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 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 Revealed Based on the Cell Line Data
Cell Pathway Regulation BRAF/MEK/MAPK signaling pathway Inhibition hsa04010
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
BCPAP cells Thyroid Homo sapiens (Human) CVCL_0153
SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
CAL62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
In Vivo Model Athymic nude mouse PDX xenografts model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting assay; Immunoprecipitation assy
Experiment for
Drug Resistance		 SRB staining assay; Promega assay
Mechanism Description Activation of the Mitogen Activated Protein (MAP) Kinase pathway was increased in all four of the dasatinib-resistant cell lines, likely due to B-Raf and c-Raf dimerization. Furthermore, MAP2K1/MAP2K2 (MEK1/2) inhibition restored sensitivity in all four of the dasatinib-resistant cell lines, and overcome acquired resistance to dasatinib in the RAS-mutant Cal62 cell line, in vivo. Together, these studies demonstrate that acquisition of the c-Src gatekeeper mutation and MAP Kinase pathway signaling play important roles in promoting resistance to the Src inhibitor, dasatinib.
References
Ref 1 Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant CancersCancer Cell. 2015 Sep 14;28(3):384-98. doi: 10.1016/j.ccell.2015.08.002. Epub 2015 Sep 3.
Ref 2 Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trialClin Cancer Res. 2014 Jan 15;20(2):490-8. doi: 10.1158/1078-0432.CCR-13-1311. Epub 2013 Oct 31.
Ref 3 Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant. Int J Clin Oncol. 2023 May;28(5):654-663.
Ref 4 Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer. Sci Rep. 2022 May 14;12(1):8008.
Ref 5 Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinibCancer Biol Ther. 2014 Sep;15(9):1239-47. doi: 10.4161/cbt.29687. Epub 2014 Jul 14.
Ref 6 ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR InhibitorMol Cancer Ther. 2015 Dec;14(12):2831-9. doi: 10.1158/1535-7163.MCT-15-0497. Epub 2015 Oct 5.
Ref 7 Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft modelsJ Exp Clin Cancer Res. 2014 Jun 17;33(1):52. doi: 10.1186/1756-9966-33-52.
Ref 8 Increase in constitutively active MEK1 species by introduction of MEK1 mutations identified in cancersBiochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):62-70. doi: 10.1016/j.bbapap.2018.05.004. Epub 2018 May 9.
Ref 9 Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trialLancet Oncol. 2019 Jul;20(7):1011-1022. doi: 10.1016/S1470-2045(19)30277-3. Epub 2019 May 28.
Ref 10 Oncogenic MAP2K1 mutations in human epithelial tumorsCarcinogenesis. 2012 May;33(5):956-61. doi: 10.1093/carcin/bgs099. Epub 2012 Feb 10.
Ref 11 Selumetinib overcomes ITGA2-induced 5-fluorouracil resistance in colorectal cancer. Int Immunopharmacol. 2024 Aug 20;137:112487.
Ref 12 Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted TherapyMol Cancer Res. 2016 Feb;14(2):207-15. doi: 10.1158/1541-7786.MCR-15-0321. Epub 2015 Nov 18.
Ref 13 Characteristics of lung cancers harboring NRAS mutationsClin Cancer Res. 2013 May 1;19(9):2584-91. doi: 10.1158/1078-0432.CCR-12-3173. Epub 2013 Mar 20.
Ref 14 Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinomaCancer Res. 2008 Jul 15;68(14):5524-8. doi: 10.1158/0008-5472.CAN-08-0099.
Ref 15 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 16 Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathwayPLoS One. 2011;6(12):e28973. doi: 10.1371/journal.pone.0028973. Epub 2011 Dec 14.
Ref 17 Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancersJ Clin Oncol. 2008 May 1;26(13):2139-46. doi: 10.1200/JCO.2007.14.4956. Epub 2008 Apr 7.
Ref 18 Turk J Haematol. 2016 Mar 5;33(1):41-7. doi: 10.4274/tjh.2014.0010. Epub 2014 May 21.
Ref 19 A kinase inhibitor screen reveals MEK1/2 as a novel therapeutic target to antagonize IGF1R-mediated antiestrogen resistance in ERalpha-positive luminal breast cancer. Biochem Pharmacol. 2022 Oct;204:115233.
Ref 20 Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian CancerJ Clin Oncol. 2015 Dec 1;33(34):4099-105. doi: 10.1200/JCO.2015.62.4726. Epub 2015 Aug 31.
Ref 21 Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistanceClin Cancer Res. 2012 Jul 1;18(13):3552-61. doi: 10.1158/1078-0432.CCR-11-3086. Epub 2012 May 1.
Ref 22 The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid CancerMol Cancer Ther. 2016 Aug;15(8):1952-63. doi: 10.1158/1535-7163.MCT-15-0702. Epub 2016 May 24.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.