Drug Information

Drug (ID: DG00344) and It's Reported Resistant Information
Name
Pembrolizumab
Indication
In total 11 Indication(s)
Melanoma [ICD-11: 2C30]
Approved
[1]
Diffuse large B-cell lymphoma [ICD-11: 2A81]
Application submitted
[1]
Breast cancer [ICD-11: 2C60]
Phase 3
[1]
Colorectal cancer [ICD-11: 2B91]
Phase 3
[1]
Esophageal cancer [ICD-11: 2B70]
Phase 3
[1]
Liver cancer [ICD-11: 2C12]
Phase 3
[1]
Lung cancer [ICD-11: 2C25]
Phase 3
[1]
Renal cell carcinoma [ICD-11: 2C90]
Phase 3
[1]
Ovarian cancer [ICD-11: 2C73]
Phase 2
[1]
Prostate cancer [ICD-11: 2C82]
Phase 2
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Melanoma [ICD-11: 2C30]
[1]
Target Programmed cell death protein 1 (PD-1) PDCD1_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
TTD Drug ID
D08ANZ
DrugBank ID
DB09037
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
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [1]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61R
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 7F68
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.46
TM score: 0.94384
Amino acid change:
Q61R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
G
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
R
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
S
S
K
K
S
D
90
|
F
F
A
A
D
D
I
I
N
N
L
L
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
D
D
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
T
T
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
H
H
E
E
L
L
A
A
K
K
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
E
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
Q
Q
Y
Y
R
R
M
M
K
K
170
|
K
-
L
-
N
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Circulating tumour DNA (ctDNA) analysis; Whole genome plasma DNA sequencing assay
Experiment for
Drug Resistance		 Computer tomography (CT) assay; Positron emission tomography assay
Mechanism Description Mutations in NRAS have been found in 8-26% of patients with acquired resistance to BRAF inhibitors. We analysed the presence of NRASQ61k and NRASQ61R in the ctDNA extracted from 7 melanoma patients with progressive disease who had previously responded to treatment with vemurafenib (n = 2) or dabrafenib/trametinib (n = 5). Two samples were positive for NRASQ61k and one sample had an NRASQ61R mutation, all three were derived from patients treated with dabrafenib/trametinib.
References
Ref 1 Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015 Dec 8;6(39):42008-18. doi: 10.18632/oncotarget.5788.

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