Drug Information

Drug (ID: DG01406) and It's Reported Resistant Information
Name
Nivolumab
Indication
In total 18 Indication(s)
Central nervous system lymphoma [ICD-11: 2B33]
Approved
[1]
Chronic myelogenous leukaemia [ICD-11: 2A20]
Approved
[1]
Diffuse large B-cell lymphoma [ICD-11: 2A81]
Approved
[1]
Esophageal cancer [ICD-11: 2B70]
Approved
[1]
Follicular lymphoma [ICD-11: 2A80]
Approved
[1]
Gastric adenocarcinoma [ICD-11: 2B72]
Approved
[1]
Gastric adenocarcinoma [ICD-11: 2B72]
Approved
[1]
Malignant pleural mesothelioma [ICD-11: 2C26]
Approved
[1]
Melanoma [ICD-11: 2C30]
Approved
[1]
Multiple myeloma [ICD-11: 2A83]
Approved
[1]
Non-small-cell lung cancer [ICD-11: 2C25]
Approved
[1]
Ovarian cancer [ICD-11: 2C73]
Approved
[1]
Pancreatic cancer [ICD-11: 2C10]
Approved
[1]
Prostate cancer [ICD-11: 2C82]
Approved
[1]
Recurrent glioblastoma [ICD-11: 2A00]
Approved
[1]
Renal cell carcinoma [ICD-11: 2C90]
Approved
[1]
Small-cell lung cancer [ICD-11: 2C25]
Approved
[1]
Triple negative breast cancer [ICD-11: 2C60-2C6Y]
Approved
[1]
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Melanoma [ICD-11: 2C30]
[2]
Neuroendocrine carcinoma [ICD-11: 2D4Y]
[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
D00GOV
INTEDE ID
DR2826
DrugBank ID
DB09035
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
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: Mismatch repair endonuclease PMS2 (PMS2) [3]
Sensitive Disease FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
 Disease Info 
Molecule Alteration FS-deletion
p.K706fs*19 (c.2118delG)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
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: Serine/threonine-protein kinase B-raf (BRAF) [2]
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
420
|
M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
|
H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
|
T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
|
W
W
E
E
I
I
P
P
D
D
G
G
Q
Q
I
I
T
T
V
V
460
|
G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
|
T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
|
V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
|
P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
|
N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
|
H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
|
S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
|
Q
Q
W
W
C
C
E
E
G
G
S
S
S
S
L
L
Y
Y
H
H
540
|
H
H
L
L
H
H
I
I
I
I
E
E
T
T
K
K
F
F
E
E
550
|
M
M
I
I
K
K
L
L
I
I
D
D
I
I
A
A
R
R
Q
Q
560
|
T
T
A
A
Q
Q
G
G
M
M
D
D
Y
Y
L
L
H
H
A
A
570
|
K
K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
A
A
M
M
690
|
K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
K
K
K
K
700
|
K
K
R
R
D
D
E
E
R
R
P
P
L
L
F
F
P
P
Q
Q
710
|
I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
|
S
S
L
L
P
P
K
K
I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600K (c.1798_1799delGTinsAA)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Neuroendocrine carcinoma [ICD-11: 2D4Y]
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 3 (FGFR3) [1]
Resistant Disease Primary pulmonary lymphoepithelioma-like carcinoma [ICD-11: 2D4Y.Z]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model KB-3-1 cells Lung Homo sapiens (Human) CVCL_2088
Mechanism Description Pulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.
References
Ref 1 Case Report: Anlotinib Reverses Nivolumab Resistance in Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma With FGFR3 Gene Amplification .Front Oncol. 2021 Oct 8;11:749682. doi: 10.3389/fonc.2021.749682. eCollection 2021. 10.3389/fonc.2021.749682
Ref 2 Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant MelanomaClin Cancer Res. 2019 Feb 15;25(4):1272-1279. doi: 10.1158/1078-0432.CCR-18-1680. Epub 2019 Jan 10.
Ref 3 Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair DeficiencyJ Clin Oncol. 2016 Jul 1;34(19):2206-11. doi: 10.1200/JCO.2016.66.6552. Epub 2016 Mar 21.

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