产品说明书

Veliparib

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Chemical Structure| 912444-00-9 同义名 : ABT-888;NSC 737664
CAS号 : 912444-00-9
货号 : A164131
分子式 : C13H16N4O
纯度 : 98%
分子量 : 244.29
MDL号 : MFCD16661059
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: 30 mg/mL(122.8 mM)，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：

0.5% methylcellulose+0.2% Tween 80+water 5 mg/mL suspension

生物活性
靶点

  • PARP1

    PARP1, Ki:5.2 nM

  • PARP2

    PARP2, Ki:2.9 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. Veliparib is a potent PARP inhibitor with Ki values of 5.2nM and 2.9nM for PARP-1 and PARP-2 (measured by recombinant human PARP), respectively[1], which has shown promise in combination with chemotherapy in preclinical studies. In presence of 5μM Veliparib for 15, 30 and 240 min, the level of PAR protein, the product catalyzed by PARP, was dramatically decreased by Veliparib in both irradiated and non-irradiated H460 lung cancer cells to nearly undetectable levels. 10-fold decrease in cell survival at 6Gy irradiation can be observed 8 days latere after treatment with 5μM Veliparib for 6h and then washed off. At 6h after 5Gy irradiation, the addition of 5μM Veliparib significantly increased the percentage of cells containingγ-H2AX foci, a marker of double-stranded DNA breaks. 3Gy irradiation combined with 5μM Veliparib showed a 2.8-fold increase in apoptosis, whereas Veliparib alone showed no increase in apoptosis and 3 Gy irradiation increased apoptosis 2-fold. Similar pattern of increase in autophagic cells can be seen. Treatment with Veliparib, 25mg/kg, i.p., for 5 consecutive days improved tumor growth delay in nude mice implanted H460 tumors[2]. Significant inhibition in the level of PAR can be observed in B16F10 flank tumor xenograft mice dosed with Veliparib (25 and 3.125 mg/kg/d, p.o., b.i.d. x 2) with or without temozolomide, which showed the inhibition by Veliparib on PARP activity in vivo[1].
作用机制 Veliparib more favorably interacts with the space between Gln319 and Glu322 in PARP-2 over the Glu763 and Asp766 in PARP-1 in the catalytic domain.[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
697 Growth Inhibition Assay IC50=29.0235 μM SANGER
A2780 Growth Inhibition Assay IC50=30.7457 μM SANGER
A388 Growth Inhibition Assay IC50=21.9091 μM SANGER
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
NCT00770471 Brain and Central Nervous Syst... 展开 >>em Tumors 收起 << Phase 1 Completed - United States, Alabama ... 展开 >> UAB Comprehensive Cancer Center Birmingham, Alabama, United States, 35294-3410 United States, California UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115 United States, Georgia Winship Cancer Institute of Emory University Atlanta, Georgia, United States, 30322 United States, Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Massachusetts Massachusetts General Hospital Boston, Massachusetts, United States, 02114 United States, Michigan Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, North Carolina Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina, United States, 27157-1096 United States, Ohio Cleveland Clinic Taussig Cancer Center Cleveland, Ohio, United States, 44195 United States, Pennsylvania Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104-4283 UPMC Cancer Centers Pittsburgh, Pennsylvania, United States, 15232 United States, Wisconsin University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin, United States, 53792-6164 收起 <<
NCT00526617 Non-hematologic Malignancies ... 展开 >> Metastatic Melanoma Breast Cancer Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer Hepatocellular Carcinoma 收起 << Phase 1 Completed - -
NCT01419548 Neoplasms Phase 1 Withdrawn - United States, Maryland ... 展开 >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 United States, Pennsylvania University of Pittsburgh Cancer Center Pittsburgh, Pennsylvania, United States 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.09mL

0.82mL

0.41mL

20.47mL

4.09mL

2.05mL

40.94mL

8.19mL

4.09mL
参考文献

[1]Donawho CK, Luo Y, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37.

[2]Albert JM, Cao C, et al. Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res. 2007 May 15;13(10):3033-42.

[3]Steffen JD, Brody JR, et al. Structural Implications for Selective Targeting of PARPs. Front Oncol. 2013 Dec 20;3:301.

[4]Kinders RJ, Hollingshead M, et al. Preclinical modeling of a phase 0 clinical trial: qualification of a pharmacodynamic assay of poly (ADP-ribose) polymerase in tumor biopsies of mouse xenografts. Clin Cancer Res. 2008;14(21):6877-85.

[5]To C, Kim EH, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res (Phila). 2014;7(7):698-707.