Drug Information

Drug (ID: DG01757) and It's Reported Resistant Information
Name
Navitoclax/Trametinib
Synonyms
Navitoclax/Trametinib
    Click to Show/Hide
Type(s) of Resistant Mechanism of This Drug
  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
Colon cancer [ICD-11: 2B90]
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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) [1]
Sensitive Disease Colon cancer [ICD-11: 2B90.1]
 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
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420
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M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
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H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
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T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
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W
W
E
E
I
I
P
P
D
D
G
G
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I
I
T
T
V
V
460
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G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
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T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
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V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
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P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
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N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
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H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
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S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
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Q
Q
W
W
C
C
E
E
G
G
S
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S
L
L
Y
Y
H
H
540
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H
H
L
L
H
H
I
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I
E
E
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F
F
E
E
550
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M
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D
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I
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560
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T
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A
A
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G
G
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M
D
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Y
L
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A
A
570
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K
K
S
S
I
I
I
I
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H
R
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L
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580
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N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
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T
T
590
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V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
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V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
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F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
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M
M
A
A
P
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E
E
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V
I
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M
M
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D
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630
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K
K
N
N
P
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Y
Y
S
S
F
F
Q
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S
D
D
V
V
640
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Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
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M
M
T
T
G
G
Q
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L
L
P
P
Y
Y
S
S
N
N
I
I
660
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N
N
N
N
R
R
D
D
Q
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I
I
I
I
F
F
M
M
V
V
670
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G
G
R
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G
G
Y
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L
L
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P
P
D
D
L
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S
S
680
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K
K
V
V
R
R
S
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N
N
C
C
P
P
K
K
A
A
M
M
690
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K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
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K
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700
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K
K
R
R
D
D
E
E
R
R
P
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L
L
F
F
P
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Q
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710
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I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
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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
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
A549 cells Lung Homo sapiens (Human) CVCL_0023
A2058 cells Skin Homo sapiens (Human) CVCL_1059
HPAF-II cells Pancreatic Homo sapiens (Human) CVCL_0313
H23 cells Lung Homo sapiens (Human) CVCL_1547
WiDR cells Colon Homo sapiens (Human) CVCL_2760
SW1573 cells Lung Homo sapiens (Human) CVCL_1720
KHM-5M cells Pleural effusion Homo sapiens (Human) CVCL_2975
WM793 cells N.A. Homo sapiens (Human) CVCL_8787/CVCL_5414
SkMEL-2 cells Skin Homo sapiens (Human) CVCL_0069
PANC 0203 cells Pancreas Homo sapiens (Human) CVCL_1633
MOR/CPR cells Lung Homo sapiens (Human) CVCL_2620
MM415 cells Lymph node Homo sapiens (Human) CVCL_2608
HTC-C3 cells Pleural effusion Homo sapiens (Human) CVCL_2273
HCC364 cells Lung Homo sapiens (Human) CVCL_5134
H2347 cells Lung Homo sapiens (Human) CVCL_1550
Calu-1 cells Lung Homo sapiens (Human) CVCL_0608
CAL-12T cells Lung Homo sapiens (Human) CVCL_1105
In Vivo Model NOD-SCID female mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; qPCR
Experiment for
Drug Resistance		 CellTiter-Glo assay; Caspase3/7-Glo iuminescent assay
References
Ref 1 The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapiesNat Genet. 2015 Mar;47(3):250-6. doi: 10.1038/ng.3218. Epub 2015 Feb 9.

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