|2-[4-((3S)-3-哌啶基)苯基]-2H-吲唑-7-甲酰胺-4-甲苯磺酸盐|CsnPharm

CAS No.: 1038915-73-9

Niraparib tosylate/尼拉帕尼对苯甲磺酸盐 Catalog No. CSN17416

Synonyms: MK-4827 tosylate;Niraparib Tosylate;MK-4827 (tosylate)

MK-4827 tosylate is a selective inhibitor of PARP1/PARP2 with IC50 of 3.8 nM/2.1 nM and with great activity in cancer cells with mutant BRCA-1 and BRCA-2 and > 330-fold selective against PARP3, V-PARP and Tank1.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 PARP1

IC50:3.8nM PARP2

IC50:2.1nM
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 Tosylate is the tosylate form of MK-4827. 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]

动物研究

剂量

Rat^[4]: 3 mg/kg (i.v.), 5 mg/kg (p.o.) Mice: 25 mg/kg, 50 mg/kg^[2] (p.o.), 100 mg/kg^[2] (p.o.)

给药途径

i.v., p.o.

动物药代数据

Animal	Rats^[4]	Dogs^[4]
Dose	3 mg/kg (i.v.) 5 mg/kg (p.o.)	1 mg/kg (i.v.) 3 mg/kg (p.o.)
Administration	i.v. p.o.	i.v. p.o.
F	27% (p.o.)	57% (p.o.)
AUC_0-inf	5.7 µM·h (i.v.) 2.5 µM·h (p.o.)
T_1/2	3.4 h	5.7 h
AUC_0→inf		1.8 µM·h (i.v.) 3.0 µM·h (p.o.)
T_max	2 h	0.5 h
CL	28 ml/min/kg (i.v.)	31 ml/min/kg (i.v.)
Vd_ss	6.9 L/kg	12.3 L/kg

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.
[4] MK-4827

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.0301 mL
- 10.1504 mL
- 20.3009 mL
- 5 mM
- 0.4060 mL
- 2.0301 mL
- 4.0602 mL
- 10 mM
- 0.2030 mL
- 1.0150 mL
- 2.0301 mL

技术信息

CAS号

1038915-73-9

储存条件

粉末: Keep in dark place,Inert atmosphere,Room temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C26H28N4O4S

运输

蓝冰

分子量

492.59

别名

MK-4827 tosylate;Niraparib Tosylate;MK-4827 (tosylate);MK-4827;Zejula;尼拉帕尼对苯甲磺酸盐

溶解度

DMSO	98.0 mg/mL (198.9 mM)
Water	Insoluble
Ethanol	Insoluble

动物实验配方

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

靶点	Description	IC50
PARP1		IC50:3.8nM
PARP2		IC50:2.1nM

Niraparib tosylate/尼拉帕尼对苯甲磺酸盐 Catalog No. CSN17416

靶点选择性

请登录您的专属账户

确认信息