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Niraparib hydrochloride (MK-4827 hydrochloride) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC50s of 3.8 and 2.1 nM, respectively. Niraparib hydrochloride leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity[1][2][3].

PARP-2: 2.1 nM (IC₅₀); PARP-1: 3.8 nM (IC₅₀); V-PARP: 330 nM (IC₅₀); TANK-1: 570 nM (IC₅₀); PARP-3: 1300 nM (IC₅₀)

[1] Jones P, et al. Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85. DOI:10.1021/jm901188v
[2] Bridges KA, et al. Niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Oncotarget. 2014 Jul 15;5(13):5076-86. DOI:10.18632/oncotarget.2083
[3] Wang L, et al. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation. Invest New Drugs. 2012 Dec;30(6):2113-20. DOI:10.1007/s10637-011-9770-x
[4] Mirza MR, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. DOI:10.1056/NEJMoa1611310