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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H14F2N6O
Molecular Weight 380.3509
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TALAZOPARIB

SMILES

CN1N=CN=C1[C@@H]2[C@H](NC3=CC(F)=CC4=C3C2=NNC4=O)C5=CC=C(F)C=C5

InChI

InChIKey=HWGQMRYQVZSGDQ-HZPDHXFCSA-N
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

HIDE SMILES / InChI

Molecular Formula C19H14F2N6O
Molecular Weight 380.3509
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Talazoparib (BMN 673) demonstrates excellent potency, inhibiting PARP1 and PARP2 enzyme activity. It inhibits PARP-mediated PARylation in a whole-cell assay and prevents proliferation of cancer cells carrying mutant BRCA1/2. Talazoparib is orally available, displaying favorable pharmacokinetic properties and remarkable antitumor efficacy in the BRCA1 mutant MX-1 breast cancer xenograft model following oral administration as a single-agent or in combination with chemotherapy agents such as temozolomide and cisplatin. Medivation (a subsidiary of Pfizer) is developing talazoparib (MDV 3800, formerly BMN 673 and LT 673) for the treatment of genetically defined cancers. On October 16, 2018, the FDA approved talazoparib (TALZENNA, Pfizer Inc.) for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2‑negative locally advanced or metastatic breast cancer.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.
2010 Oct
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
2012 Nov 1
Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone.
2014 Sep
PARP inhibitors: A new era of targeted therapy.
2015 May
Patents
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:12:12 UTC 2019
Edited
by admin
on Mon Oct 21 20:12:12 UTC 2019
Record UNII
9QHX048FRV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TALAZOPARIB
INN   USAN  
USAN   INN  
Official Name English
BMN 673
Code English
TALAZOPARIB [INN]
Common Name English
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)-
Systematic Name English
TALAZOPARIB [USAN]
Common Name English
BMN-673
Code English
(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
Systematic Name English
LT-673
Code English
TALAZOPARIB [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C62554
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
WHO-ATC L01XX60
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
NDF-RT N0000191623
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
Code System Code Type Description
CAS
1207456-01-6
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
PRIMARY
EVMPD
SUB180394
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
PRIMARY
INN
9868
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
PRIMARY
NCI_THESAURUS
C95733
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
PRIMARY
ChEMBL
CHEMBL3137320
Created by admin on Mon Oct 21 20:12:12 UTC 2019 , Edited by admin on Mon Oct 21 20:12:12 UTC 2019
PRIMARY
Related Record Type Details
BINDER->LIGAND
In vitro, protein binding of talazoparib is 74% and is independent of talazoparib concentration.
BINDING
TRANSPORTER -> SUBSTRATE
Co-administration with BCRP inhibitors may increase talazoparib exposure.
TRANSPORTER -> SUBSTRATE
Co-administration of talazoparib with certain P-gp inhibitors including amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil in the clinical studies (PRP-001, PRP-002, ABRAZO and EMBRACA) increased talazoparib exposure by 44.7%, in conjunction with an increased rate of Talzenna dose reductions (41%).
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC