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Purity: ≥98%
Talazoparib (formerly known as BMN-673 and MDV-3800; trade name: Talzenna), is a a novel, highly potent PARP1/2 [poly(ADP-ribose) polymerase] inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. Talazoparib is a novel PARP inhibitor with an IC50 of 0.58 nM in a test conducted without cells. It attaches itself specifically to PARP, blocking the base-excision repair pathway that PARP uses to repair single strand breaks in DNA. This increases the rate at which DNA strand breaks accumulate, encourages genomic instability, and ultimately results in apoptosis. The FDA approved talazoparib on October 16, 2018, for the treatment of patients with germline BRCA mutations who have metastatic or locally advanced breast cancer.
| Targets |
PARP2 ( Ki = 0.87 nM ); PARP1 ( Ki = 1.2 nM )
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In order to determine the PARP inhibitor Ki, enzyme assays were carried out in 96-well FlashPlate using 0.5 U PARP1 enzyme, 0.25x activated DNA, 0.2 mCi [3H] NAD, and 5 mmol/L cold NAD (Sigma) in a final volume of 50 mL reaction buffer that contained 10% glycerol (v/v), 25 mmol/L HEPES, 12.5 mmol/L MgCl2, 50 mmol/L KCl, 1 mmol/L dithiothreitol (DTT), and 0.01% NP-40 (v/v), and pH 7.6. NAD was added to the PARP reaction mixture, either with or without inhibitors, to start the reaction, and it was then incubated for one minute at room temperature. The reaction was then stopped by adding 50 microliter of ice-cold 20% trichloroacetic acid (TCA) to each well. After the plate was sealed and shaken for an additional 120 minutes at room temperature, centrifugation was performed. Top-Count was used to determine the radioactive signal bound to the FlashPlate. The Michaelis-Menten equation was used to calculate PARP1 Km at different substrate concentrations (ranging from 1 to 100 mmol/L NAD). Using the formula Ki ¼ IC50/[1þ (substrate)/Km], compound Ki was computed from the enzyme inhibition curve. Using the same assay protocol, Km for the PARP2 enzyme and compound Ki were found. However, instead of using 30 ng of PARP2, 0.25x activated DNA, 0.2 mCi [3H] NAD, and 20 mmol/L cold NAD, the reaction was run for 30 minutes at room temperature.
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| Cell Assay |
A panel of 11 SCLC cell lines (IC50=1.7 to 15 nmol/L), all of which fall within clinically feasible ranges, demonstrate BMN 673's strong inhibitory action. Furthermore, PI3K pathway activity and DNA repair protein expression are correlated with BMN673 sensitivity.
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| References |
| Molecular Formula |
C19H14F2N6O
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| Molecular Weight |
380.35
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| Exact Mass |
380.12
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| Elemental Analysis |
C, 60.00; H, 3.71; F, 9.99; N, 22.10; O, 4.21
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| CAS # |
1207456-01-6
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| Related CAS # |
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| Appearance |
White solid powder
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| SMILES |
CN1C(=NC=N1)[C@@H]2[C@H](NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F
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| InChi Key |
HWGQMRYQVZSGDQ-HZPDHXFCSA-N
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| InChi Code |
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
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| Chemical Name |
(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
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| Synonyms |
BMN 673; BMN673; MDV-3800; MDV 3800; MDV3800; BMN-673; LT673; LT 673; LT-673; Talazoparib; trade name: Talzenna
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (13.15 mM) in 10% DMAC 6% Solutol HS-15 84% PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Solubility in Formulation 2: ≥ 2.5 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 1.25 mg/mL (3.29 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 0.5 mg/mL (1.31 mM) (saturation unknown) in 2% DMSO + 40% PEG300 + 5% Tween80 + 53% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 0.25 mg/mL (0.66 mM) (saturation unknown) in 1% DMSO + 99% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6292 mL | 13.1458 mL | 26.2916 mL | |
| 5 mM | 0.5258 mL | 2.6292 mL | 5.2583 mL | |
| 10 mM | 0.2629 mL | 1.3146 mL | 2.6292 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03772925 | Active Recruiting |
Drug: Belinostat Drug: Pevonedistat |
Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia |
National Cancer Institute (NCI) |
June 20, 2019 | Phase 1 |
| NCT02137759 | Active Recruiting |
Drug: Standard Temozolomide Drug: Belinostat |
Glioblastoma Multiforme of Brain |
Emory University | May 7, 2014 | Phase 2 |
| NCT05170334 | Recruiting | Drug: Binimetinib Drug: Belinostat |
Metastatic Uveal Melanoma | H. Lee Moffitt Cancer Center and Research Institute |
December 15, 2021 | Phase 2 |
| NCT04747236 | Recruiting | Drug: Belinostat Drug: Pralatrexate |
PTCL | University of Virginia | February 19, 2021 | Phase 2 |
| NCT02737046 | Recruiting | Drug: Belinostat Drug: Zidovudine |
ATLL Adult T-cell Leukemia- Lymphoma |
University of Miami | December 12, 2016 | Phase 2 |
BMN 673 is a potent PARP inhibitor.Clin Cancer Res.2013 Sep 15;19(18):5003-15. |
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A, siRNAs targeting homologous recombination genes sensitize to PARP1/2 inhibitors.Clin Cancer Res.2013 Sep 15;19(18):5003-15. |
BMN 673 exhibits antitumor activity against a BRCA-mutant tumor model in mice.Clin Cancer Res.2013 Sep 15;19(18):5003-15. |
BMN 673 potentiates the effects of DNA-damaging cytotoxic agents.Clin Cancer Res.2013 Sep 15;19(18):5003-15. |
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