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]。