Talazoparib tosylate
(Synonyms: BMN 673ts) 目录号 : GC37728Talazoparib tosylate (BMN 673ts) 是一种新型,高效,有可口服活性的 PARP1/2 抑制剂,抑制PARP1的IC50 值为 0.57 nM。
Cas No.:1373431-65-2
Sample solution is provided at 25 µL, 10mM.
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Talazoparib tosylate (BMN 673ts) is a novel, potent and orally available PARP1/2 inhibitor with an IC50 of 0.57 nM for PARP1. IC50: 0.57 nM (PARP1)[1]
Talazoparib is a potent PARP1/2 inhibitor (PARP1 IC50=0.57 nM), it has no effect on PARG activity at concentrations up to 1 μM. Talazoparib binds to PARP1 with a dissociation constant (KD) of 0.29 nM. Talazoparib inhibits PARP1 and -2 to a similar extent, with Kis of 1.20 and 0.85 nM, respectively. Talazoparib selectively targets tumor cells with BRCA1, BRCA2, or PTEN gene defects with 20- to more than 200-fold greater potency than existing PARP1/2 inhibitors. Talazoparib targets tumor cells with homologous recombination gene defects. Tumor models that are either BRCA1-deficient (MX-1 and SUM149) or BRCA2-deficient (Capan-1) are profoundly sensitive to Talazoparib. Talazoparib induces nuclear γ-H2AX foci at concentrations as low as 100 pM[1].
Talazoparib is readily orally bioavailable, with more than 40% absolute oral bioavailability in rats when dosed in carboxylmethyl cellulose. Oral administration of Talazoparib elicits remarkable antitumor activity; xenografted tumors that carry defects in DNA repair due to BRCA mutations or PTEN deficiency are profoundly sensitive to oral Talazoparib treatment at well-tolerated doses in mice. Synergistic or additive antitumor effects are also found when Talazoparib is combined with temozolomide, SN38, or platinum drugs[1].
Talazoparib tosylate (BMN 673ts) 是一种新型、有效且可口服的 PARP1/2 抑制剂,对 PARP1 的 IC50 为 0.57 nM。 IC50:0.57 nM (PARP1)[1]
Talazoparib 是一种有效的 PARP1/2 抑制剂(PARP1 IC50=0.57 nM),它在浓度高达 1 μM 时对 PARG 活性没有影响。 Talazoparib 以 0.29 nM 的解离常数 (KD) 结合 PARP1。 Talazoparib 以相似的程度抑制 PARP1 和 -2,Kis 分别为 1.20 和 0.85 nM。 Talazoparib 选择性靶向具有 BRCA1、BRCA2 或 PTEN 基因缺陷的肿瘤细胞,效力比现有的 PARP1/2 抑制剂高 20 至 200 多倍。 Talazoparib 靶向具有同源重组基因缺陷的肿瘤细胞。 BRCA1 缺陷(MX-1 和 SUM149)或 BRCA2 缺陷(Capan-1)的肿瘤模型对 Talazoparib 极为敏感。 Talazoparib 在低至 100 pM 的浓度下诱导核 γ-H2AX 灶[1]。
Talazoparib 具有口服生物利用度,当以羧甲基纤维素给药时,大鼠的绝对口服生物利用度超过 40%。 Talazoparib 的口服给药具有显着的抗肿瘤活性;由于 BRCA 突变或 PTEN 缺陷而携带 DNA 修复缺陷的异种移植肿瘤对小鼠口服耐受良好剂量的 Talazoparib 治疗非常敏感。 Talazoparib 与替莫唑胺、SN38 或铂类药物联合使用时,也发现了协同或相加的抗肿瘤作用[1]。
[1]. Shen Y, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res. 2013 Sep 15;19(18):5003-15.
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。 |
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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 | ||||||||||
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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.