Talazoparib (BMN 673)
Catalog No.S7048 Synonyms: LT-673
Molecular Weight(MW): 380.35
Talazoparib (BMN 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.
Purity & Quality Control
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Biological Activity
| Description | Talazoparib (BMN 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Most potent and selective PARPi reported thus far. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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| 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] |
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| Cell Data |
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| Assay |
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| 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] |
Protocol
| Animal Research: |
- Collapse
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Solubility (25°C)
| In vitro | DMSO | 38 mg/mL warmed (99.9 mM) |
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| Water | Insoluble | |
| Ethanol | 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.
Chemical Information
| Molecular Weight | 380.35 |
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| Formula |
C19H14F2N6O
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| CAS No. | 1207456-01-6 |
| Storage | powder |
| in solvent | |
| Synonyms | LT-673 |
Bio Calculators
Molarity Calculator
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Dilution Calculator
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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
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Molarity Calculator
Clinical Trial Information
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|---|
| NCT03974217 | Recruiting | Drug: Talazoparib | Leukemia | Dana-Farber Cancer Institute|Pfizer | August 1 2019 | Phase 1 |
| NCT03901469 | Recruiting | Drug: ZEN003694|Drug: Talazoparib | Triple Negative Breast Cancer | Zenith Epigenetics|Pfizer | June 26 2019 | Phase 2 |
| NCT03911973 | Recruiting | Drug: Gedatolisib|Drug: Talazoparib | TNBC - Triple-Negative Breast Cancer | Kari Wisinski|Pfizer|Big Ten Cancer Research Consortium | April 17 2019 | Phase 1|Phase 2 |
| NCT03875313 | Recruiting | Drug: CB-839|Drug: Talazoparib | Solid Tumor|Clear Cell Renal Cell Carcinoma|TNBC - Triple-Negative Breast Cancer|Colorectal Cancer|CRC|RCC|ccRCC | Calithera Biosciences Inc | March 22 2019 | Phase 1|Phase 2 |
| NCT03672773 | Recruiting | Drug: Talazoparib|Drug: Temozolomide | Recurrent Extensive Stage Small Cell Lung Carcinoma|Refractory Extensive Stage Small Cell Lung Carcinoma | Jonsson Comprehensive Cancer Center|Translational Research in Oncology|National Cancer Institute (NCI) | October 31 2018 | Phase 2 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
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Question 1:
Which solvent do you recommend to dilute the inhibitor for in vivo study in mice?
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Answer:
BMN673 (S7048) can be dissolved in vehicle (10% DMAc, 6% Solutol, and 84% PBS) according to the paper: http://clincancerres.aacrjournals.org/content/19/18/5003.full. Quote from Method and Material section "Xenograft experiments: BMN 673 (various doses as indicated), or vehicle (10% DMAc, 6% Solutol, and 84% PBS) was administered by oral gavage"
