| Identification | Back Directory | [Name]
(S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxaMide | [CAS]
1038915-64-8 | [Synonyms]
CS-787
Zejula
EOS-62286
MK-4827 (HCl)
MK-4827 (hydrochloride)
Niraparib hydrochloride
MK-4827, Niraparib HCl salt
Niraparib Tosylate Monohydrate
Niraparib(MK4827) hydrochloride
2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide,hydrochloride
(3S)-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl]piperidinium chloride
(S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide dihydrochloride
2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]-, hydrochloride (1:1) | [Molecular Formula]
C19H20N4O | [MDL Number]
MFCD20502397 | [MOL File]
1038915-64-8.mol | [Molecular Weight]
320.388 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
Niraparib is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib is characterized by acceptable pharmacokinetics in rats with plasma clearance of 28 (mL/min)/kg, very high volume of distribution (Vdss=6.9 L/kg), long terminal half-life (t1/2=3.4 h), and excellent bioavailability, F = 65%[1]. Niraparib enhances radiation response of p53 mutant Calu-6 tumor in both cases, with the single daily dose of 50 mg/kg being more effective than 25 mg/kg given twice daily[3]. | [IC 50]
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) | [References]
[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 |
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