产品说明书

Niraparib

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	同义名 :	MK-4827( 尼拉帕尼) ;MK-4827
	CAS号 :	1038915-60-4
	货号 :	A298513
	分子式 :	C₁₉H₂₀N₄O
	纯度 :	98%
	分子量 :	320.39
	MDL号 :	MFCD17779309
	存储条件：	粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 25 mg/mL(78.03 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
	动物实验配方：	IP 2% DMSO+2% Tween80+40% PEG300+water 1 mg/mL clear PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点	PARP1 PARP1, IC50:3.8 nM PARP2 PARP2, IC50:2.1 nM
描述	PARP1, also called as Poly(ADP-ribose) polymerase, is involved in the signaling of DNA damage. It can recognize and bind DNA single or double-strand breaks, thus possessing various cellular function, including regulation of apoptosis and chromosome stability, gene amplification and transcription, as well as cell division and differentiation. PARP-2 is the closest homolog of PARP1 (~62% similarity in catalytic domain) and compensates for PARP-1 activity in DNA single-strand break. MK-4827 is potent inhibitor of PARP1 and PARP2 with IC50 values of 3.8nM and 2.1nM (measured by PARP isoform TCA assays), respectively, at least a 100-fold selectivity over PARP-3, V-PARP, and tankyrase-1. MK-4827 inhibited PARP activity with EC50 of 4nM and preferentially suppressed proliferation of MDA-MB-436 cells carrying BRCA-1 mutation with CC50 value of 18nM and CAPAN-1 cells carrying BRCA-2 mutantation with CC50 value of 90nM. Oral treatment with MK-4827 at either 100 mg/kg q.d. or 50 mg/kg b.i.d. for 33 days repressed tumor growth in a BRCA-1 mutant MDA-MB-436 xenograft model^[1].Oral administration of MK-4827 at a dose of 50mg/kg once daily radiosensitized all four tumors regardless of the p53 status, including Calu-6, H460, A549 and MDA-MB-231, with reduced PAR levels in tumors^[2].
作用机制	MK-4827 is a nicotinamide derivate, which can compete with NAD+ for the PARP catalytic site.^[3]

细胞研究
细胞系	浓度	检测类型	检测时间	活动说明	数据源
A2780 cells		Function assay		Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay	25761096
A549 cells		Cytotoxicity assay	5-7 days	Cytotoxicity against human A549 cells transfected with BRCA2 shRNA assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=0.011 μM	25761096
BT20 cells		Cytotoxicity assay	5-7 days	Cytotoxicity against human BT20 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50=2.2 μM	25761096

临床研究
NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT03705156	Platinum-sensitive Relapsed Ov... 展开 >>arian Cancer 收起 <<	Phase 3	Recruiting	June 8, 2020	-
NCT03709316	Ovarian Cancer	Phase 3	Recruiting	June 30, 2021	-
NCT03574779	Ovarian Cancer	Phase 2	Recruiting	June 2020	United States, Massachusetts ... 展开 >> Dana-Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 United States, Oklahoma Stephenson Cancer Center Recruiting Oklahoma City, Oklahoma, United States, 73104 收起 <<

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

3.12mL

0.62mL

0.31mL

15.61mL

3.12mL

1.56mL

31.21mL

6.24mL

3.12mL

参考文献

[1]Jones P, Altamura S, 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.

[2]Wang L, Mason KA, 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.

[3]Javle M, Curtin NJ, et al. The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. Ther Adv Med Oncol. 2011 Nov;3(6):257-67.

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靶点

靶点	数值

PARP1	PARP1, IC50:3.8 nM
PARP2	PARP2, IC50:2.1 nM