Talazoparib (BMN 673)

Catalog No.S7048 Batch:S704808

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Technical Data

Formula

 

C19H14F2N6O
 
Molecular Weight 380.35 CAS No. 1207456-01-6
Solubility (25°C)* In vitro DMSO 76 mg/mL (199.81 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Talazoparib (BMN 673, LT-673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3.
Targets
PARP1 [1]
(Cell-free assay)
0.57 nM
In vitro

BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. BMN 673 selectively kills cancer cells with BRCA-1 or BRCA-2 mutations. BMN 673 demonstrates single-agent cytotoxicityin BRCA-1 mutant (MX-1, IC50 = 0.3 nM) and BRCA-2 mutant cells (Capan-1, IC50 = 5 nM). In contrast, in MRC-5 normal human fibroblastand other tumor cell lines with wild-type BRCA-1 and BRCA-2 genes, IC50 of BMN 673 ranges between 90 nM and 1.9 μM. [1]

In cultured human cancer cells, BMN 673 also significantly enhances the cytotoxic efficacy of both Temozolomide and SN-38. Off-target molecular screening did not identify significant non-specific activity for this class of PARP inhibitors. [2]
In vivo

In rat pharmacokinetic studies, BMN 673 displays >50% oralbioavailability and pharmacokinetic properties that enable singledaily dosing. In MX-1 xenograft tumor model studies, daily oral dosingof BMN 673 significantly enhances the antitumor effects ofcytotoxic therapies in a dose-dependent manner. [2]
Features Most potent and selective PARPi reported thus far.

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    MDA-MB-436 cells

  • Concentrations

    10 uM

  • Incubation Time

    7 days

  • Method

    Cells were treated with increasing doses of talazoparib for 7 days and subjected to cell viability assays to derive IC50 values.
Animal Study:

[2]
  • Animal Models

    MX-1 model (BRCA-1 deficient)

  • Dosages

    0.33 mg/kg/day, once daily

  • Administration

    Oral

Customer Product Validation

, , Clin Cancer Res, 2017, 23(13):3405-3415

Data from [Data independently produced by , , Nature, 2018, 559(7713):285-289]

Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(14):3711-3720]

Data from [Data independently produced by , , J Neuroinflammation, 2016, 13(1):254.]

Selleck's Talazoparib (BMN 673) has been cited by 228 publications

Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 10.1038/s41586-024-07217-2] PubMed: 38509368
Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO [ bioRxiv, 2024, 2024.01.20.576487.] PubMed: 38328189
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response [ Nat Genet, 2023, 55(8):1311-1323] PubMed: 37524790
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA [ Nucleic Acids Res, 2023, gkad150] PubMed: 36940725
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA [ Nucleic Acids Research, 2023, 51(13)-] PubMed: None
Real-time imaging of drug-induced trapping of cellular topoisomerases and poly-ADP-ribose) polymerase 1 at the single-molecule level [ Nucleic Acids Res, 2023, 51(18):e97] PubMed: 37670571
PRMT blockade induces defective DNA replication stress response and synergizes with PARP inhibition [ Cell Rep Med, 2023, 4(12):101326] PubMed: 38118413
Widespread BRCA1/2-independent homologous recombination defects are caused by alterations in RNA-binding proteins [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101255] PubMed: 37909041
Bispecific antibodies targeting EGFR/Notch enhance the response to talazoparib by decreasing tumour-initiating cell frequency [ Theranostics, 2023, 13(11):3641-3654] PubMed: 37441599

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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