Drug Information

Drug (ID: DG01689) and It's Reported Resistant Information
Name
Everolimus/Selumetinib
Synonyms
Everolimus/Selumetinib
    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
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) [1]
Sensitive Disease Brain glioma [ICD-11: 2A00.0]
 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
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420
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M
M
D
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R
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430
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H
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G
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S
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E
E
D
D
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N
N
R
R
M
M
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440
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T
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L
G
G
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450
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460
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G
G
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G
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470
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Y
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480
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A
A
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M
M
L
L
N
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V
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A
A
490
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T
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P
P
Q
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L
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A
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500
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E
E
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510
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I
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520
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L
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530
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540
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550
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560
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570
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I
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580
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590
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I
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F
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A
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600
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E
K
K
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R
W
W
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G
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610
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F
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L
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620
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A
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630
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640
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A
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650
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G
G
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L
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Y
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N
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660
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N
N
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670
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G
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680
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K
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R
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N
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C
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A
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M
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690
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L
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700
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710
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L
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720
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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 DBTRG cells Brain Homo sapiens (Human) CVCL_1169
SF9427 cells N.A. Homo sapiens (Human) N.A.
SF8628 cells Brain Homo sapiens (Human) CVCL_IT46
SF188 cells Brain Homo sapiens (Human) CVCL_6948
BT40 cells N.A. Homo sapiens (Human) N.A.
AM-38 cells Brain Homo sapiens (Human) CVCL_1070
In Vivo Model NSG mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description Combination therapy in BRAFV600E-mutant human glioma cells enhances cell cycle arrest and apoptosis and reduces proliferation compared to monotherapy.
Lung cancer [ICD-11: 2C25]
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 Hras (HRAS) [2]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 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 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
Bladder cancer [ICD-11: 2C94]
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 Hras (HRAS) [2]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 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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20
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30
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50
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60
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70
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80
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C
C
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90
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D
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I
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100
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110
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G
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120
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130
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A
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140
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150
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160
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170
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M
M
S
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D
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G
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K
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K
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K
180
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K
K
S
S
K
K
T
T
K
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C
C
V
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I
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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
References
Ref 1 BRAF Status in Personalizing Treatment Approaches for Pediatric GliomasClin Cancer Res. 2016 Nov 1;22(21):5312-5321. doi: 10.1158/1078-0432.CCR-15-1101. Epub 2016 May 23.
Ref 2 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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