Talazoparib tosylate
(Synonyms: BMN 673ts) 目录号 : GC37728
Talazoparib tosylate（BMN 673ts）是一种有效的具有口服活性的PARP1/2抑制剂，是Talazoparib的甲苯磺酸盐形式。Talazoparib抑制PARP1的IC50值为0.57nM。
Cas No.:1373431-65-2
Sample solution is provided at 25 µL, 10mM.
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Talazoparib tosylate (BMN 673ts) is a potent and orally active PARP1/2 inhibitor, which is the tosylate salt form of Talazoparib. Talazoparib inhibits PARP1 with an IC50 value of 0.57 nM[1]. PARP1 is a DNA repair enzyme that is important for repairing single-strand breaks[2]. Talazoparib has selective antitumor activity[3].
In vitro, Brca1−/− BR5FVB1-Akt cells treated with Talazoparib (0.1-100 nM) for 72 h inhibited cell proliferation in a dose-dependent manner[4]. Talazoparib treatment of DT40 and DU145 cells for 72 h had significant cytotoxic effects, with IC50 values of 4 nM and 11 nM, respectively[5]. Talazoparib treatment of four human head and neck cancer cell lines (UMSCC-5, -6, -12, -38) showed a relative inhibitory effect on cell growth, with an IC50 range of 0.1-10 μM[6].
In vivo, oral treatment of mice bearing subcutaneous MX-1 tumor xenografts with Talazoparib (0.33mg/kg) significantly inhibited tumor growth and reduced intracellular ADP-ribose (PAR) levels in tumor cells[7].
References:
[1] Shen Y, Rehman F L, Feng Y, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency[J]. Clinical Cancer Research, 2013, 19(18): 5003-5015.
[2] Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling[J]. Nature reviews Molecular cell biology, 2017, 18(10): 610-621.
[3] Ng R. Niraparib (Zejula), A Small Molecule, PARP1/2 Inhibitor for Treating Breast, Ovarian, and Pancreatic Cancers[J]. Current Drug Synthesis, 2022: 231-251.
[4] Huang J, Wang L, Cong Z, et al. The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1−/− murine model of ovarian cancer[J]. Biochemical and biophysical research communications, 2015, 463(4): 551-556.
[5] Murai J, Huang S Y N, Renaud A, et al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib[J]. Molecular cancer therapeutics, 2014, 13(2): 433-443.
[6] Shin D D, Ratikan J, Manivong K, et al. The poly (ADP-ribose) polymerase inhibitor BMN 673 has single agent activity and augments cytotoxicity of radiation in human head and neck tumor cell line in vitro: a novel strategy for radiosensitization in head and neck cancer[J]. Cancer Research, 2013, 73(8_Supplement): 1595-1595.
[7] Shen Y, Rehman F L, Feng Y, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency[J]. Clinical Cancer Research, 2013, 19(18): 5003-5015.
Talazoparib tosylate（BMN 673ts）是一种有效的具有口服活性的PARP1/2抑制剂，是Talazoparib的甲苯磺酸盐形式。Talazoparib抑制PARP1的IC50值为0.57nM[1]。PARP1是一种DNA修复酶，对于修复单链断裂非常重要[2]。Talazoparib具有选择性抗肿瘤活性[3]。
在体外，Talazoparib（0.1-100 nM）处理Brca1−/− BR5FVB1-Akt细胞72 h，以剂量依赖性方式抑制了细胞增殖[4]。Talazoparib处理DT40和DU145细胞72 h，具有显著的细胞毒性作用，IC50值分别为4nM和11nM[5]。Talazoparib处理四种人头颈癌细胞系（UMSCC-5、-6、-12、-38），均对细胞生长表现出了相对抑制作用，IC50范围为0.1-10μM[6]。
在体内，Talazoparib（0.33 mg/kg）通过口服治疗带有皮下MX-1肿瘤异种移植物的小鼠，显著抑制了肿瘤生长，降低了肿瘤细胞内ADP-核糖（PAR）水平[7]。
| Cas No. | 1373431-65-2 | SDF | |
| 别名 | BMN 673ts | ||
| Canonical SMILES | O=C1NN=C2C3=C1C=C(F)C=C3N[C@H](C4=CC=C(F)C=C4)[C@H]2C5=NC=NN5C.O=S(C6=CC=C(C)C=C6)(O)=O | ||
| 分子式 | C26H22F2N6O4S | 分子量 | 552.55 |
| 溶解度 | DMSO: ≥ 108 mg/mL (195.46 mM) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8098 mL | 9.049 mL | 18.0979 mL |
| 5 mM | 0.362 mL | 1.8098 mL | 3.6196 mL |
| 10 mM | 0.181 mL | 0.9049 mL | 1.8098 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Talazoparib to treat BRCA-positive breast cancer
Drugs Today (Barc) 2019 Jul;55(7):459-467.PMID:31347614DOI:10.1358/dot.2019.55.7.3015642
Talazoparib tosylate (BMN-673, Talzenna; Pfizer) is an oral poly [ADP-ribose] polymerase (PARP) inhibitor (PARPi) that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of germline BRCA-mutated locally advanced or metastatic breast cancer (BC). In preclinical and clinical studies, talazoparib exerted superior efficacy and offered a significant clinical benefit in advanced or metastatic BC patients harboring germline BRCA mutations compared with other PARPi and standard chemotherapy regimens through the concept of synthetic lethality. Thus, this review provides insight into the results of preclinical and clinical studies, highlights the current challenges of talazoparib and suggests innovative approaches to further improve its clinical efficacy and expand the use of talazoparib in advanced BC and/or triple-negative BC treatments beyond BRCA mutations.