Drug Information

Drug (ID: DG01670) and It's Reported Resistant Information
Name
Talazoparib
Synonyms
Talazoparib; 1207456-01-6; BMN-673; BMN673; BMN 673; Talzenna; Talazoparib (BMN 673); UNII-9QHX048FRV; (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one; LT-673; 9QHX048FRV; (8s,9r)-5-Fluoro-8-(4-Fluorophenyl)-9-(1-Methyl-1h-1,2,4-Triazol-5-Yl)-2,7,8,9-Tetrahydro-3h-Pyrido[4,3,2-De]phthalazin-3-One; (11S,12R)-7-fluoro-11-(4-fluorophenyl)-12-(2-methyl-1,2,4-triazol-3-yl)-2,3,10-triazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8-tetraen-4-one; (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3H-pyrido[4,3,2-de]phthalazine-3-one; Talazoparib [USAN:INN]; BMN-673 8R,9S; 4pjt; 2YQ; Talazoparib(BMN-673); Talazoparib (USAN/INN); Talazoparib (BMN-673); 3H-Pyrido(4,3,2-de)phthalazin-3-one, 5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-, (8S,9R)-; GTPL8313; SCHEMBL2299348; CHEMBL3137320; AOB5705; BMN673,BMN-673; AMY27900; EX-A1356; BDBM50084621; MFCD22666357; NSC767125; ZINC72318110; ZINC138126699; CS-0937; DB11760; NSC-767125; QC-4556; NCGC00390231-01; AC-30927; AS-57491; HY-16106; LT 00673; S7048; SW219655-1; X5821; D10732; A892079; Q25100990; Q27453411; (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one;BMN-673
    Click to Show/Hide
Indication
In total 1 Indication(s)
Non-small-cell lung cancer [ICD-11: 2C25]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Ovarian cancer [ICD-11: 2C73]
[2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
2
IsoSMILES
CN1C(=NC=N1)[C@@H]2[C@H](NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F
InChI
InChI=1S/C19H14F2N6O/c1-27-18(22-8-23-27)15-16(9-2-4-10(20)5-3-9)24-13-7-11(21)6-12-14(13)17(15)25-26-19(12)28/h2-8,15-16,24H,1H3,(H,26,28)/t15-,16-/m1/s1
InChIKey
HWGQMRYQVZSGDQ-HZPDHXFCSA-N
PubChem CID
135565082
TTD Drug ID
D0I1QI
INTEDE ID
DR00366
DrugBank ID
DB11760
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  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: Oxalosuccinate decarboxylase (IDH1) [1]
Sensitive Disease Brain glioma [ICD-11: 2A00.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R132H (c.395G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 6BKX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.88  Å
PDB: 4UMX
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.46
TM score: 0.85834
Amino acid change:
R132H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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40
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60
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A
A
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E
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70
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G
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C
A
A
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I
T
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80
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E
E
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90
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Q
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N
G
G
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I
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100
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R
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N
I
I
L
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G
G
G
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F
F
R
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110
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E
E
A
A
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I
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C
C
K
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120
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L
L
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G
G
W
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I
130
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I
I
G
G
R
H
H
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A
A
Y
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G
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D
D
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Y
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140
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R
R
A
A
T
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D
D
F
F
V
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G
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150
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G
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Y
Y
T
T
P
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160
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D
D
G
G
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T
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K
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V
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Y
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L
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170
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H
H
N
N
F
F
E
E
E
E
G
G
G
G
G
G
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A
A
180
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M
M
G
G
M
M
Y
Y
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N
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D
D
K
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I
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190
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E
E
D
D
F
F
A
A
H
H
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F
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M
M
200
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A
A
L
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G
G
W
W
P
P
L
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Y
Y
L
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210
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S
S
T
T
K
K
N
N
T
T
I
I
L
L
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K
K
K
Y
Y
220
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D
D
G
G
R
R
F
F
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I
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230
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I
I
Y
Y
D
D
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Q
Y
Y
K
K
S
S
Q
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F
F
240
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E
E
A
A
Q
Q
K
K
I
I
W
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Y
Y
E
E
H
H
R
R
250
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L
L
I
I
D
D
D
D
M
M
V
V
A
A
Q
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A
A
M
M
260
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K
K
S
S
E
E
G
G
G
G
F
F
I
I
W
W
A
A
C
C
270
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K
K
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
280
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S
S
V
V
A
A
Q
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G
G
Y
Y
G
G
S
S
L
L
G
G
290
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M
M
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
300
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G
G
K
K
T
T
V
V
E
E
A
A
E
E
A
A
A
A
H
H
310
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G
G
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
M
M
Y
Y
320
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Q
Q
K
K
G
G
Q
Q
E
E
T
T
S
S
T
T
N
N
P
P
330
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I
I
A
A
S
S
I
I
F
F
A
A
W
W
T
T
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R
G
G
340
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L
L
A
A
H
H
R
R
A
A
K
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L
L
D
D
N
N
N
N
350
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K
K
E
E
L
L
A
A
F
F
F
F
A
A
N
N
A
A
L
L
360
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E
E
E
E
V
V
S
S
I
I
E
E
T
T
I
I
E
E
A
A
370
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G
G
F
F
M
M
T
T
K
K
D
D
L
L
A
A
A
A
C
C
380
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I
I
K
K
G
G
L
L
P
P
N
N
V
V
Q
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R
R
S
S
390
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D
D
Y
Y
L
L
N
N
T
T
F
F
E
E
F
F
M
M
D
D
400
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K
K
L
L
G
G
E
E
N
N
L
L
K
K
I
I
K
K
L
L
410
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A
A
Q
Q
A
A
K
K
L
L
S
S
L
L
E
E
H
H
H
H
420
|
H
H
H
H
H
H
H
H
H
H
H
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
IDH1 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model Female athymic nu/nu mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Promega assay
Mechanism Description The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.
Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]
Sensitive Disease Brain glioma [ICD-11: 2A00.0]
 Disease Info 
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.93  Å
PDB: 5GIR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6IO0
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.64
TM score: 0.30204
Amino acid change:
R132C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
S
-
K
-
K
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I
-
S
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G
-
G
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10
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V
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V
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M
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G
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20
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40
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H
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Y
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L
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N
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R
50
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60
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A
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A
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E
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A
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70
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80
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100
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110
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R
120
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K
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P
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I
I
130
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I
I
G
G
S
C
H
H
A
A
Y
Y
G
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D
D
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Y
140
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150
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160
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Q
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K
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L
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V
170
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N
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F
-
E
-
E
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G
-
G
-
G
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A
180
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M
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M
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N
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I
190
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E
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200
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210
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Y
220
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230
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240
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G
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270
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N
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Y
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D
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D
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D
280
|
-
S
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A
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Y
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G
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G
290
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M
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M
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300
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E
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E
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A
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A
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H
310
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G
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T
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Y
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R
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M
-
Y
320
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-
Q
-
K
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G
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E
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T
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S
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T
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N
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P
330
|
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I
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A
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I
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A
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W
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G
340
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-
L
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A
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H
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R
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A
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L
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D
-
N
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N
350
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K
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E
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L
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A
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F
-
F
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A
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N
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A
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L
360
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E
-
E
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V
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S
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I
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E
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T
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E
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A
370
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G
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F
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M
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A
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A
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380
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I
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L
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N
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V
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S
390
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-
D
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Y
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L
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N
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T
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F
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E
-
F
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M
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D
400
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-
K
-
L
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G
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E
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N
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L
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K
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I
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K
-
L
410
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-
A
-
Q
-
A
-
K
-
L
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
IDH1 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model Female athymic nu/nu mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Promega assay
Mechanism Description The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.
Colon cancer [ICD-11: 2B90]
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: Oxalosuccinate decarboxylase (IDH1) [1]
Sensitive Disease Colon cancer [ICD-11: 2B90.1]
 Disease Info 
Molecule Alteration Missense mutation
p.R132H (c.395G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 6BKX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.88  Å
PDB: 4UMX
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.46
TM score: 0.85834
Amino acid change:
R132H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
S
S
K
K
K
K
I
I
S
S
G
G
G
G
S
S
10
|
V
V
V
V
E
E
M
M
Q
Q
G
G
D
D
E
E
M
M
T
T
20
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R
R
I
I
I
I
W
W
E
E
L
L
I
I
K
K
E
E
K
K
30
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L
L
I
I
F
F
P
P
Y
Y
V
V
E
E
L
L
D
D
L
L
40
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H
H
S
S
Y
Y
D
D
L
L
G
G
I
I
E
E
N
N
R
R
50
|
D
D
A
A
T
T
N
N
D
D
Q
Q
V
V
T
T
K
K
D
D
60
|
A
A
A
A
E
E
A
A
I
I
K
K
K
K
H
H
N
N
V
V
70
|
G
G
V
V
K
K
C
C
A
A
T
T
I
I
T
T
P
P
D
D
80
|
E
E
K
K
R
R
V
V
E
E
E
E
F
F
K
K
L
L
K
K
90
|
Q
Q
M
M
W
W
K
K
S
S
P
P
N
N
G
G
T
T
I
I
100
|
R
R
N
N
I
I
L
L
G
G
G
G
T
T
V
V
F
F
R
R
110
|
E
E
A
A
I
I
I
I
C
C
K
K
N
N
I
I
P
P
R
R
120
|
L
L
V
V
S
S
G
G
W
W
V
V
K
K
P
P
I
I
I
I
130
|
I
I
G
G
R
H
H
H
A
A
Y
Y
G
G
D
D
Q
Q
Y
Y
140
|
R
R
A
A
T
T
D
D
F
F
V
V
V
V
P
P
G
G
P
P
150
|
G
G
K
K
V
V
E
E
I
I
T
T
Y
Y
T
T
P
P
S
S
160
|
D
D
G
G
T
T
Q
Q
K
K
V
V
T
T
Y
Y
L
L
V
V
170
|
H
H
N
N
F
F
E
E
E
E
G
G
G
G
G
G
V
V
A
A
180
|
M
M
G
G
M
M
Y
Y
N
N
Q
Q
D
D
K
K
S
S
I
I
190
|
E
E
D
D
F
F
A
A
H
H
S
S
S
S
F
F
Q
Q
M
M
200
|
A
A
L
L
S
S
K
K
G
G
W
W
P
P
L
L
Y
Y
L
L
210
|
S
S
T
T
K
K
N
N
T
T
I
I
L
L
K
K
K
K
Y
Y
220
|
D
D
G
G
R
R
F
F
K
K
D
D
I
I
F
F
Q
Q
E
E
230
|
I
I
Y
Y
D
D
K
K
Q
Q
Y
Y
K
K
S
S
Q
Q
F
F
240
|
E
E
A
A
Q
Q
K
K
I
I
W
W
Y
Y
E
E
H
H
R
R
250
|
L
L
I
I
D
D
D
D
M
M
V
V
A
A
Q
Q
A
A
M
M
260
|
K
K
S
S
E
E
G
G
G
G
F
F
I
I
W
W
A
A
C
C
270
|
K
K
N
N
Y
Y
D
D
G
G
D
D
V
V
Q
Q
S
S
D
D
280
|
S
S
V
V
A
A
Q
Q
G
G
Y
Y
G
G
S
S
L
L
G
G
290
|
M
M
M
M
T
T
S
S
V
V
L
L
V
V
C
C
P
P
D
D
300
|
G
G
K
K
T
T
V
V
E
E
A
A
E
E
A
A
A
A
H
H
310
|
G
G
T
T
V
V
T
T
R
R
H
H
Y
Y
R
R
M
M
Y
Y
320
|
Q
Q
K
K
G
G
Q
Q
E
E
T
T
S
S
T
T
N
N
P
P
330
|
I
I
A
A
S
S
I
I
F
F
A
A
W
W
T
T
R
R
G
G
340
|
L
L
A
A
H
H
R
R
A
A
K
K
L
L
D
D
N
N
N
N
350
|
K
K
E
E
L
L
A
A
F
F
F
F
A
A
N
N
A
A
L
L
360
|
E
E
E
E
V
V
S
S
I
I
E
E
T
T
I
I
E
E
A
A
370
|
G
G
F
F
M
M
T
T
K
K
D
D
L
L
A
A
A
A
C
C
380
|
I
I
K
K
G
G
L
L
P
P
N
N
V
V
Q
Q
R
R
S
S
390
|
D
D
Y
Y
L
L
N
N
T
T
F
F
E
E
F
F
M
M
D
D
400
|
K
K
L
L
G
G
E
E
N
N
L
L
K
K
I
I
K
K
L
L
410
|
A
A
Q
Q
A
A
K
K
L
L
S
S
L
L
E
E
H
H
H
H
420
|
H
H
H
H
H
H
H
H
H
H
H
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
IDH1 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model Female athymic nu/nu mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Promega assay
Mechanism Description The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.
References
Ref 1 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivitySci Transl Med. 2017 Feb 1;9(375):eaal2463. doi: 10.1126/scitranslmed.aal2463.
Ref 2 Poly (ADP-Ribose) Polymerase Inhibitor Olaparib-Resistant BRCA1-Mutant Ovarian Cancer Cells Demonstrate Differential Sensitivity to PARP Inhibitor Rechallenge. Cells. 2024 Nov 7;13(22):1847.

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