Mefuparib (hydrochloride)

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]. In Vitro: 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].
In Vivo: 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 T_1/2 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 T_1/2 of 2.16-2.7 hours and a C _max of 114-608 ng/mL for cynomolgus monkeys^[1].