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Niraparib tosylate

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Chemical Structure| 1038915-73-9 同义名 : 尼拉帕利 ;MK-4827 tosylate;MK-4827 (tosylate)
CAS号 : 1038915-73-9
货号 : A159121
分子式 : C26H28N4O4S
纯度 : 99%+
分子量 : 492.59
MDL号 : MFCD28167748
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(213.16 mM)，配合低频超声，并水浴加热至45℃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

H2O: 1 mg/mL(2.03 mM)，水浴加热至45℃助溶
动物实验配方：
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 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]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.03mL

0.41mL

0.20mL

10.15mL

2.03mL

1.02mL

20.30mL

4.06mL

2.03mL
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