Talazoparib (BMN-673) 是一种高效的，具有口服活性的PARP 1/2抑制剂。Talazoparib 抑制 PARP1 和 PARP2 酶活性的Ki值分别为 1.2 nM 和 0.87 nM。Talazoparib 具有抗肿瘤活性。
| 生物活性 | Talazoparib (BMN-673) is a highly potent, orally activePARP1/2inhibitor.Talazoparib inhibitsPARP1andPARP2enzyme activity withKis of 1.2 nM and 0.87 nM, respectively. Talazoparib has antitumor activity[1]. |
| IC50& Target[1] | PARP2 0.87 nM (Ki) | PARP1 1.2 nM (Ki) |
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体外研究
(In Vitro) | Talazoparib shows an EC50of 2.51 nM in cellular PARylation assay[1].
Talazoparib shows EC50s of 0.3 nM, 5 nM and 0.31 for MX-1 cells (BRCA1 mutant), Capan-1 cells (BRCA2 mutant) and MRC-5 cells (normal)[1].
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体内研究
(In Vivo) | Talazoparib (0.33 mg/kg; i.g.; once daily; for 28 days) exhibits antitumor activity against BRCA1 mutant breast cancer model in mice[1].
Talazoparib exhibits moderate oral bioavailability (rat 56%) and Cmax(rat 7948 ng/mL) following oral administration (rat 10 mg/kg)[1].
Talazoparib exhibits the terminal elimination half-life (rat 2.25 h) due to plasma clearance (2 mL/min/kg) following intravenous administration (rat 5 mg/kg)[1].
| Animal Model: | Female athymic nu/nu mice (8-10 weeks old), with MX-1 xenograft-bearing mice[1] | | Dosage: | 0.33 mg/kg | | Administration: | Oral gavage, once daily, for 28 days | | Result: | Significantly inhibited xenograft MX-1 tumor growth. |
| Animal Model: | Sprague-Dawley rats[1] | | Dosage: | 5mg/kg for i.v.; 10 mg/kg for oral (Pharmacokinetic Analysis) | | Administration: | Intravenous administration and oral administration | | Result: | Oral bioavailability (56%), Cmax(7948 ng/mL), T1/2(2.25 h). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(65.73 mM;Need ultrasonic) 配制储备液 | 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 |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMAC 6% Solutol HS-15 84% PBS Solubility: 5 mg/mL (13.15 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.57 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.57 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: 1.25 mg/mL (3.29 mM); Suspended solution; Need ultrasonic 4. 请依序添加每种溶剂： 2% DMSO 40%PEG300 5%Tween-80 53% saline Solubility: ≥ 0.5 mg/mL (1.31 mM); Clear solution 5. 请依序添加每种溶剂： 1% DMSO 99% saline Solubility: ≥ 0.25 mg/mL (0.66 mM); Clear solution *以上所有助溶剂都可在本网站选购。
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