| Identification | Back Directory | [Name]
MK-4827 (tosylate) | [CAS]
1038915-73-9 | [Synonyms]
Niraparib TOS
Niraparib TsOH
Niraparib Tosylate
MK-4827 (tosylate)
MK-4827(Niraparib) tosylate
Niraparib(MK-4827) tosylate
MK-4827, Niraparib TsOH salt
niraparib p-toluenesulfonate
MK-4827 (tosylate) ISO 9001：2015 REACH
NIRAPARIB TOSYLATE;MK 4827 TOSYLATE;MK4827 TOSYLATE
(3S)-3-[4-[7-(Aminocarbonyl)-2H-indazol-2-yl]phenyl]piperidine tosylate
2H-Indazole-7-carboxamide,2-[4-[(3S)-3-piperidinyl]phenyl]-,4-methylbenzenesulfonate(1:1) | [Molecular Formula]
C26H28N4O4S | [MDL Number]
MFCD28167748 | [MOL File]
1038915-73-9.mol | [Molecular Weight]
492.59 |
| Chemical Properties | Back Directory | [Melting point ]
>142oC (dec.) | [storage temp. ]
-20°C Freezer | [solubility ]
Methanol (Slightly) | [form ]
Solid | [color ]
Off-White to Pale Yellow | [InChIKey]
LCPFHXWLJMNKNC-XOIICWPPNA-N | [SMILES]
S(C1C=CC(C)=CC=1)(O)(=O)=O.C(C1=CC=CC2=CN(C3C=CC([C@H]4CNCCC4)=CC=3)N=C12)(=O)N |&1:23,r| |
| Hazard Information | Back Directory | [Description]
Niraparib tosylate (MK-4827 tosylate) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively; with significant activity in cancer cells with mutant BRCA-1 and BRCA-2; >330-fold selective against PARP3, V-PARP, and Tank1. Niraparib tosylate leads to inhibition of repair of DNA damage, activates apoptosis, and shows anti-tumor activity. | [Uses]
Niraparib is a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. | [in vitro]
In a whole-cell assay, Niraparib (MK-4827) tosylate hydrate inhibits PARP activity with EC50=4 nM and EC90=45 nM. Niraparib tosylate hydrate inhibits the proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. Niraparib tosylate hydrate displays excellent PARP 1 and 2 inhibition with IC50=3.8 and 2.1 nM, respectively, and in a whole-cell assay.
Niraparib tosylate hydrate inhibits PARP within 15 minutes of treatment, reaching about 85% inhibition in the A549 cells at 1 h and about 55% inhibition at 1 h for the H1299 cells. | [in vivo]
Niraparib (MK-4827) is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (MK-4827) is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (MK-4827) 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 (MK-4827) 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] PHILIP JONES*. 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]. Journal of Medicinal Chemistry, 2009, 52 22: 7170-7185. DOI: 10.1021/jm901188v
[2] YUAN YUAN. Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP.[J]. Journal of Hematology & Oncology, 2011, 4: 16. DOI: 10.1186/1756-8722-4-16
[3] LI WANG. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation.[J]. Investigational New Drugs, 2012: 2113-2120. DOI: 10.1007/s10637-011-9770-x
[4] MIRZA M, MONK B, HERRSTEDT J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.[J]. The New England Journal of Medicine, 2016, 75 1: 0. DOI: 10.1056/nejmoa1611310 |
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