Mefuparib hydrochloride (MPH) 是一种具有口服活性的，底物竞争性和选择性的 PARP1/2 抑制剂，IC50 分别为 3.2 nM 和 1.9 nM。Mefuparib hydrochloride 诱导细胞凋亡 (apoptosis)，并在体内外具有显着的抗癌活性。
Mefuparib hydrochloride (MPH) is an orally active, substrate-competitive and selective PARP1/2 inhibitor with IC50s of 3.2 nM and 1.9 nM, respectively. Mefuparib hydrochloride induces apoptosis and possesses prominent anticancer activity in vitro and in vivo[1][2].
Mefuparib hydrochloride (1-10 μM; 48 hours) causes cell apoptosis[1]. Mefuparib hydrochloride (MPH; 1-10 μM; 24 hours) causes V-C8 cells into typical G2/M arrest[1]. Mefuparib hydrochloride (1-10 μM; 24 hours) causes the accumulation of DSB marked by the increased levels of γH2AX in the MDA-MB-436 (BRCA1-/-) cells in a concentration-dependent manner[1]. Mefuparib hydrochloride exerts potent in vitro proliferation-inhibitory effects on cancer cells derived from different human tissues with an average IC50 of 2.16 μM (0.12 μM~3.64 μM)[1]. Mefuparib hydrochloride inhibits PARP3 (IC50>10 μM), PARP6 (IC50>10 μM), TNKS1 (IC50=1.6 μM), TNKS2 (IC50=1.3 μM)[1].
Mefuparib hydrochloride (MPH; 40-160 mg/kg; orally; once every other day; for 21 days) displays dose- and time-dependent killing on V-C8 xenografts accompanied by complete disappearance of some xenografts, especially in the high-dose group[1]. Mefuparib hydrochloride (160 mg/kg; orally; once every other day; for 21 days) inhibits the growth of the BR-05-0028 breast patient-derived xenograft (PDX) without obvious loss of body weight[1]. Mefuparib hydrochloride (10, 20, 40 mg/kg; oral) has a T1/2 of 1.07-1.3 hours and a C max of 116-725 ng/mL for SD rats[1]. Mefuparib hydrochloride (5, 10, 20 mg/kg; oral) has a T1/2 of 2.16-2.7 hours and a C max of 114-608 ng/mL for cynomolgus monkeys[1].
[1]. He JX, et al. Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution. Oncotarget. 2017 Jan 17;8(3):4156-4168.
[2]. Nie D, et al. Cancer-Cell-Membrane-Coated Nanoparticles with a Yolk-Shell Structure Augment Cancer Chemotherapy. Nano Lett. 2020 Feb 12;20(2):936-946.
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