Drug Information

Drug (ID: DG01641) and It's Reported Resistant Information
Name
Enasidenib
Synonyms
Enasidenib; 1446502-11-9; AG-221; AG-221 (Enasidenib); CC-90007 Free Base; IDHIFA; UNII-3T1SS4E7AG; AG 221; 2-Methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-ylamino)propan-2-ol; CC-90007; 3T1SS4E7AG; 2-methyl-1-((4-(6-(trifluoromethyl)pyridin-2-yl)-6-((2-(trifluoromethyl)pyridin-4-yl)amino)-1,3,5-triazin-2-yl)amino)propan-2-ol; 2-Methyl-1-[(4-[6-(Trifluoromethyl)pyridin-2-Yl]-6-{[2-(Trifluoromethyl)pyridin-4-Yl]amino}-1,3,5-Triazin-2-Yl)amino]propan-2-Ol; 2-methyl-1-[[4-[6-(trifluoromethyl)pyridin-2-yl]-6-[[2-(trifluoromethyl)pyridin-4-yl]amino]-1,3,5-triazin-2-yl]amino]propan-2-ol; 2-Propanol, 2-methyl-1-[[4-[6-(trifluoromethyl)-2-pyridinyl]-6-[[2-(trifluoromethyl)-4-pyridinyl]amino]-1,3,5-triazin-2-yl]amino]-; 2-Propanol, 2-methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-; Enasidenib [INN]; enasidenibum; AG221; 2-methyl-1-({4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl}amino)propan-2-ol; AG-221(Enasidenib); AG-221; Enasidenib; Enasidenib; AG-221; Enasidenib (USAN/INN); Enasidenib [USAN:INN]; GTPL8960; CHEMBL3989908; SCHEMBL15102202; EX-A654; CHEBI:145374; HMS3873D03; AMY38698; BCP16041; BDBM50503251; MFCD29472245; NSC788120; s8205; AKOS026750439; ZINC222731806; CCG-269476; CS-5017; DB13874; NSC-788120; SB19193; NCGC00479249-03; NCGC00479249-05; AC-31318; AS-75164; HY-18690; FT-0700204; D10901; A857662; J-690181; Q27077182; B0084-470859; AG-221; AG 221; AG221; CC-90007; CC 90007; CC90007; 69Q
    Click to Show/Hide
Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 3
[1]
Structure
Target Serine/threonine-protein kinase B-raf (BRAF) BRAF_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
6
IsoSMILES
CC(C)(CNC1=NC(=NC(=N1)C2=NC(=CC=C2)C(F)(F)F)NC3=CC(=NC=C3)C(F)(F)F)O
InChI
InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)
InChIKey
DYLUUSLLRIQKOE-UHFFFAOYSA-N
PubChem CID
89683805
ChEBI ID
CHEBI:145374
TTD Drug ID
D0M5XN
VARIDT ID
DR0574
DrugBank ID
DB13874
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
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
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [1]
Sensitive Disease FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
 Disease Info 
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIS
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.29352
Amino acid change:
R172K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
TF-1a cells Bone marrow Homo sapiens (Human) CVCL_3608
IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model NSG mouse PDX model Mus musculus
Mechanism Description Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits alpha-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation.
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [1]
Sensitive Disease FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
 Disease Info 
Molecule Alteration Missense mutation
p.R140Q (c.419G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
Mutant Type Structure Method: X-ray diffraction Resolution: 1.54  Å
PDB: 5I95
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.33
TM score: 0.99798
Amino acid change:
R140Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
TF-1a cells Bone marrow Homo sapiens (Human) CVCL_3608
IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model NSG mouse PDX model Mus musculus
Mechanism Description Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits alpha-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation.
Acute myeloid leukemia [ICD-11: 2A60]
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: Isocitrate dehydrogenase NADP 2 (IDH2) [2]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIS
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.29352
Amino acid change:
R172K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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-
R
-
I
-
K
-
V
-
A
-
K
-
P
50
|
-
V
-
V
-
E
-
M
-
D
-
G
-
D
-
E
-
M
-
T
60
|
-
R
-
I
-
I
-
W
-
Q
-
F
-
I
-
K
-
E
-
K
70
|
-
L
-
I
-
L
-
P
-
H
-
V
-
D
-
I
-
Q
-
L
80
|
-
K
-
Y
-
F
-
D
-
L
-
G
-
L
-
P
-
N
-
R
90
|
-
D
-
Q
-
T
-
D
-
D
-
Q
-
V
-
T
-
I
-
D
100
|
-
S
-
A
-
L
-
A
-
T
-
Q
-
K
-
Y
-
S
-
V
110
|
-
A
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
120
|
-
E
-
A
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
130
|
-
K
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
140
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
150
|
-
E
-
P
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
160
|
-
L
-
V
-
P
-
G
-
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
S
K
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
-
A
-
T
-
D
-
F
-
V
-
A
-
D
-
R
-
A
190
|
-
G
-
T
-
F
-
K
-
M
-
V
-
F
-
T
-
P
-
K
200
|
-
D
-
G
-
S
-
G
-
V
-
K
-
E
-
W
-
E
-
V
210
|
-
Y
-
N
-
F
-
P
-
A
-
G
-
G
-
V
-
G
-
M
220
|
-
G
-
M
-
Y
-
N
-
T
-
D
-
E
-
S
-
I
-
S
230
|
-
G
-
F
-
A
-
H
-
S
-
C
-
F
-
Q
-
Y
-
A
240
|
-
I
-
Q
-
K
-
K
-
W
-
P
-
L
-
Y
-
M
-
S
250
|
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
A
-
Y
-
D
260
|
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
-
I
270
|
-
F
-
D
-
K
-
H
-
Y
-
K
-
T
-
D
-
F
-
D
280
|
-
K
-
N
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
-
L
290
|
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
V
-
L
-
K
300
|
-
S
-
S
-
G
-
G
-
F
-
V
-
W
-
A
-
C
-
K
310
|
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
-
I
320
|
-
L
-
A
-
Q
-
G
-
F
-
G
-
S
-
L
-
G
-
L
330
|
-
M
-
T
-
S
-
V
-
L
-
V
-
C
-
P
-
D
-
G
340
|
-
K
-
T
-
I
-
E
-
A
-
E
-
A
-
A
-
H
-
G
350
|
-
T
-
V
-
T
-
R
-
H
-
Y
-
R
-
E
-
H
-
Q
360
|
-
K
-
G
-
R
-
P
-
T
-
S
-
T
-
N
-
P
-
I
370
|
-
A
-
S
-
I
-
F
-
A
-
W
-
T
-
R
-
G
-
L
380
|
-
E
-
H
-
R
-
G
-
K
-
L
-
D
-
G
-
N
-
Q
390
|
-
D
-
L
-
I
-
R
-
F
-
A
-
Q
-
M
-
L
-
E
400
|
-
K
-
V
-
C
-
V
-
E
-
T
-
V
-
E
-
S
-
G
410
|
-
A
-
M
-
T
-
K
-
D
-
L
-
A
-
G
-
C
-
I
420
|
-
H
-
G
-
L
-
S
-
N
-
V
-
K
-
L
-
N
-
E
430
|
-
H
-
F
-
L
-
N
-
T
-
T
-
D
-
F
-
L
-
D
440
|
-
T
-
I
-
K
-
S
-
N
-
L
-
D
-
R
-
A
-
L
450
|
-
G
-
R
-
Q
-
S
-
L
-
E
-
H
-
H
-
H
-
H
460
|
-
H
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
In Vivo Model Acute myeloid leukemia xenograft mouse model Mus musculus
Experiment for
Drug Resistance		 IC50 assay
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [2]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R140Q (c.419G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
Mutant Type Structure Method: X-ray diffraction Resolution: 1.54  Å
PDB: 5I95
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.33
TM score: 0.99798
Amino acid change:
R140Q
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
40
|
A
A
D
D
K
K
R
R
I
I
K
K
V
V
A
A
K
K
P
P
50
|
V
V
V
V
E
E
M
M
D
D
G
G
D
D
E
E
M
M
T
T
60
|
R
R
I
I
I
I
W
W
Q
Q
F
F
I
I
K
K
E
E
K
K
70
|
L
L
I
I
L
L
P
P
H
H
V
V
D
D
I
I
Q
Q
L
L
80
|
K
K
Y
Y
F
F
D
D
L
L
G
G
L
L
P
P
N
N
R
R
90
|
D
D
Q
Q
T
T
D
D
D
D
Q
Q
V
V
T
T
I
I
D
D
100
|
S
S
A
A
L
L
A
A
T
T
Q
Q
K
K
Y
Y
S
S
V
V
110
|
A
A
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
120
|
E
E
A
A
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
130
|
K
K
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
140
|
R
Q
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
150
|
E
E
P
P
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
160
|
L
L
V
V
P
P
G
G
W
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
K
R
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
A
A
T
T
D
D
F
F
V
V
A
A
D
D
R
R
A
A
190
|
G
G
T
T
F
F
K
K
M
M
V
V
F
F
T
T
P
P
K
K
200
|
D
D
G
G
S
S
G
G
V
V
K
K
E
E
W
W
E
E
V
V
210
|
Y
Y
N
N
F
F
P
P
A
A
G
G
G
G
V
V
G
G
M
M
220
|
G
G
M
M
Y
Y
N
N
T
T
D
D
E
E
S
S
I
I
S
S
230
|
G
G
F
F
A
A
H
H
S
S
C
C
F
F
Q
Q
Y
Y
A
A
240
|
I
I
Q
Q
K
K
K
K
W
W
P
P
L
L
Y
Y
M
M
S
S
250
|
T
T
K
K
N
N
T
T
I
I
L
L
K
K
A
A
Y
Y
D
D
260
|
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
I
I
270
|
F
F
D
D
K
K
H
H
Y
Y
K
K
T
T
D
D
F
F
D
D
280
|
K
K
N
N
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
L
L
290
|
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
V
V
L
L
K
K
300
|
S
S
S
S
G
G
G
G
F
F
V
V
W
W
A
A
C
C
K
K
310
|
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
I
I
320
|
L
L
A
A
Q
Q
G
G
F
F
G
G
S
S
L
L
G
G
L
L
330
|
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
G
G
340
|
K
K
T
T
I
I
E
E
A
A
E
E
A
A
A
A
H
H
G
G
350
|
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
E
E
H
H
Q
Q
360
|
K
K
G
G
R
R
P
P
T
T
S
S
T
T
N
N
P
P
I
I
370
|
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
L
L
380
|
E
E
H
H
R
R
G
G
K
K
L
L
D
D
G
G
N
N
Q
Q
390
|
D
D
L
L
I
I
R
R
F
F
A
A
Q
Q
M
M
L
L
E
E
400
|
K
K
V
V
C
C
V
V
E
E
T
T
V
V
E
E
S
S
G
G
410
|
A
A
M
M
T
T
K
K
D
D
L
L
A
A
G
G
C
C
I
I
420
|
H
H
G
G
L
L
S
S
N
N
V
V
K
K
L
L
N
N
E
E
430
|
H
H
F
F
L
L
N
N
T
T
T
T
D
D
F
F
L
L
D
D
440
|
T
T
I
I
K
K
S
S
N
N
L
L
D
D
R
R
A
A
L
L
450
|
G
G
R
R
Q
Q
S
L
L
E
E
H
H
H
H
H
H
H
H
H
460
|
H
H
H
H
H
H
H
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
In Vivo Model Acute myeloid leukemia xenograft mouse model Mus musculus
Experiment for
Drug Resistance		 IC50 assay
Hematologic cancer [ICD-11: 2B3Z]
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: Isocitrate dehydrogenase NADP 2 (IDH2) [3]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
 Disease Info 
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIS
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.29352
Amino acid change:
R172K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
40
|
-
A
-
D
-
K
-
R
-
I
-
K
-
V
-
A
-
K
-
P
50
|
-
V
-
V
-
E
-
M
-
D
-
G
-
D
-
E
-
M
-
T
60
|
-
R
-
I
-
I
-
W
-
Q
-
F
-
I
-
K
-
E
-
K
70
|
-
L
-
I
-
L
-
P
-
H
-
V
-
D
-
I
-
Q
-
L
80
|
-
K
-
Y
-
F
-
D
-
L
-
G
-
L
-
P
-
N
-
R
90
|
-
D
-
Q
-
T
-
D
-
D
-
Q
-
V
-
T
-
I
-
D
100
|
-
S
-
A
-
L
-
A
-
T
-
Q
-
K
-
Y
-
S
-
V
110
|
-
A
-
V
-
K
-
C
-
A
-
T
-
I
-
T
-
P
-
D
120
|
-
E
-
A
-
R
-
V
-
E
-
E
-
F
-
K
-
L
-
K
130
|
-
K
-
M
-
W
-
K
-
S
-
P
-
N
-
G
-
T
-
I
140
|
-
R
-
N
-
I
-
L
-
G
-
G
-
T
-
V
-
F
-
R
150
|
-
E
-
P
-
I
-
I
-
C
-
K
-
N
-
I
-
P
-
R
160
|
-
L
-
V
-
P
-
G
-
W
T
T
K
K
P
P
I
I
T
T
170
|
I
I
G
G
S
K
H
H
A
A
H
H
G
G
D
D
Q
Q
Y
Y
180
|
K
K
-
A
-
T
-
D
-
F
-
V
-
A
-
D
-
R
-
A
190
|
-
G
-
T
-
F
-
K
-
M
-
V
-
F
-
T
-
P
-
K
200
|
-
D
-
G
-
S
-
G
-
V
-
K
-
E
-
W
-
E
-
V
210
|
-
Y
-
N
-
F
-
P
-
A
-
G
-
G
-
V
-
G
-
M
220
|
-
G
-
M
-
Y
-
N
-
T
-
D
-
E
-
S
-
I
-
S
230
|
-
G
-
F
-
A
-
H
-
S
-
C
-
F
-
Q
-
Y
-
A
240
|
-
I
-
Q
-
K
-
K
-
W
-
P
-
L
-
Y
-
M
-
S
250
|
-
T
-
K
-
N
-
T
-
I
-
L
-
K
-
A
-
Y
-
D
260
|
-
G
-
R
-
F
-
K
-
D
-
I
-
F
-
Q
-
E
-
I
270
|
-
F
-
D
-
K
-
H
-
Y
-
K
-
T
-
D
-
F
-
D
280
|
-
K
-
N
-
K
-
I
-
W
-
Y
-
E
-
H
-
R
-
L
290
|
-
I
-
D
-
D
-
M
-
V
-
A
-
Q
-
V
-
L
-
K
300
|
-
S
-
S
-
G
-
G
-
F
-
V
-
W
-
A
-
C
-
K
310
|
-
N
-
Y
-
D
-
G
-
D
-
V
-
Q
-
S
-
D
-
I
320
|
-
L
-
A
-
Q
-
G
-
F
-
G
-
S
-
L
-
G
-
L
330
|
-
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340
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350
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360
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370
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380
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390
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400
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410
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420
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430
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440
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450
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460
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Colorectal cancer [ICD-11: 2B91]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIS
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5SVN
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.13
TM score: 0.29352
Amino acid change:
R172K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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40
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50
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60
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70
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80
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100
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110
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120
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130
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140
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150
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160
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170
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180
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190
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210
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220
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230
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240
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260
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270
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280
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290
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310
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320
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330
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340
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350
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360
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370
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380
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430
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440
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model U87MG cells Brain Homo sapiens (Human) CVCL_GP63
TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
TF-1a cells Bone marrow Homo sapiens (Human) CVCL_3608
IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model NSG mouse PDX model Mus musculus
Mechanism Description Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits alpha-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation.
References
Ref 1 AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 MutationsCancer Discov. 2017 May;7(5):478-493. doi: 10.1158/2159-8290.CD-16-1034. Epub 2017 Feb 13.
Ref 2 Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemiaBlood. 2017 Aug 10;130(6):722-731. doi: 10.1182/blood-2017-04-779405. Epub 2017 Jun 6.
Ref 3 Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: Preliminary results from KEYNOTE-0280.

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