Talazoparib (BMN 673)
For research use only.
Catalog No.S7048 Synonyms: LT-673
122 publications

CAS No. 1207456-01-6
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.
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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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: |
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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 |
Smiles | CN1C(=NC=N1)C2C(NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F |
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment) | ||||||||||
Dosage | mg/kg | Average weight of animals | g | Dosing volume per animal | ul | Number of animals | ||||
Step 2: Enter the in vivo formulation () | ||||||||||
% DMSO % % Tween 80 % ddH2O | ||||||||||
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: : mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL,)
Method for preparing in vivo formulation:Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80,mix and clarify, next add μL ddH2O,mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
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Molarity Calculator
Clinical Trial Information
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
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NCT04692662 | Not yet recruiting | Drug: talazoparib | Solid Tumors | National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) | January 8 2021 | Phase 2 |
NCT04672460 | Not yet recruiting | Drug: TALZENNA capsule|Drug: Talazoparib soft gel capsule | Advanced Solid Tumors | Pfizer | December 2020 | Phase 1 |
NCT04497116 | Recruiting | Drug: RP-3500|Drug: Talazoparib: oral PARP inhibitor | Advanced Solid Tumor Adult | Repare Therapeutics | July 22 2020 | Phase 1|Phase 2 |
NCT04337970 | Recruiting | Drug: Talazoparib|Drug: Axitinib | Kidney Cancer|Renal Cell Carcinoma|Unresectable Renal Cell Carcinoma|Metastatic Renal Cell Carcinoma | Memorial Sloan Kettering Cancer Center | April 6 2020 | Phase 1|Phase 2 |
NCT04134884 | Recruiting | Drug: Talazoparib|Drug: ASTX727 | Metastatic Breast Cancer|Triple Negative Breast Cancer|Hormone Receptor Positive Tumor | Kathy Miller|Pfizer|Astex Pharmaceuticals Inc.|Van Andel Institute Stand Up to Cancer Team|Indiana University | March 30 2020 | Phase 1 |
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"