| Size | Price | Stock | Qty |
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| 1mg |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
PARP
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|---|---|
| ln Vitro |
In a cellular PARylation experiment, (8R,9S)-Talazoparib exhibits an EC50 of 864 nM [1]. In Capan-1 cells (a BRCA2 mutation), (8R,9S)-Talazoparib had an EC50 of 1135 nM [1].
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| References | |
| Additional Infomation |
We have discovered and developed a series of novel tetrahydropyridophthalazinone compounds as inhibitors of poly(ADP-ribose) polymerases (PARP) 1 and 2. Lead compound optimization screening identified (8S,9R)-47 (taporazopanib; BMN 673; (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). This compound's unique stereospecific biphasic central intercalation structure enables it to bind extensively and uniquely to PARP1/2 proteins. (8S,9R)-47 exhibits excellent inhibitory activity, with inhibition constants Ki of 1.2 nM for PARP1 and 0.87 nM for PARP2 enzyme activity. (8S,9R)-47 inhibited PARP-mediated parylation in whole-cell experiments with an EC50 of 2.51 nM and inhibited the proliferation of cancer cells carrying mutant BRCA1/2 with EC50s of 0.3 nM (MX-1) and 5 nM (Capan-1), respectively. (8S,9R)-47 is orally available and has good pharmacokinetic (PK) characteristics. In a BRCA1 mutant MX-1 breast cancer xenograft model, it showed significant antitumor efficacy when taken orally as a monotherapy or in combination with chemotherapy drugs such as temozolomide and cisplatin. (8S,9R)-47 has completed a phase I clinical trial and is currently undergoing phase II and III clinical trials for the treatment of locally advanced and/or metastatic breast cancer carrying germline BRCA1/2 pathogenic mutations. [1]
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| Molecular Formula |
C19H14F2N6O
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|---|---|
| Molecular Weight |
380.4
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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 # |
1207456-00-5
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| Related CAS # |
Talazoparib tosylate;1373431-65-2;Talazoparib;1207456-01-6
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| PubChem CID |
135742498
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| Appearance |
White to off-white solid powder
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| LogP |
1.898
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
28
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| Complexity |
654
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| Defined Atom Stereocenter Count |
2
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| InChi Key |
HWGQMRYQVZSGDQ-HOTGVXAUSA-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-/m0/s1
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| Chemical Name |
(11R,12S)-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 |
1207456-00-5; (8R,9S)-Talazoparib; BMN-673 8R,9S; (8r,9s)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1h-1,2,4-triazol-5-yl)-8,9-dihydro-2h-pyrido[4,3,2-de]phthalazin-3(7h)-one; BMN-673 (8R,9S); CHEMBL3764816; (8R,9S)-BMN-673; LT-674;
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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 |
| 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) |
DMSO : ≥ 50 mg/mL (~131.46 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6288 mL | 13.1441 mL | 26.2881 mL | |
| 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL | |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 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.
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