描述

Veliparib (ABT-888) 维利帕尼

产品标签

Veliparib 维利帕尼；ABT-888；PARP1/ PARP2抑制剂；Temozolomide 替莫唑胺；Radiopotentiation辐射增强；chemopotentiation化疗增强；CAS：912444-00-9；

产品信息

产品名称	产品编号	规格	价格（元）
Veliparib (ABT-888) 维利帕尼	MZ3701-10MG	10mg	868
Veliparib (ABT-888) 维利帕尼	MZ3701-50MG	50mg	2428
Veliparib (ABT-888) 维利帕尼	MZ3701-100MG	100mg	4188

产品描述

维利帕尼（Veliparib），又称为ABT-888，是一种有效的PARP1和PARP2抑制剂，Ki值分别是5.2nM和2.9nM，对SIRT2没有活性。ABT-888具有良好的口服生物活性，能够穿透血脑屏障，在同源肿瘤模型和异种移植肿瘤模型中增强替莫唑胺（Temozolomide）、铂类、环磷酰胺和放射效果[1]。ABT-888具有广谱的化学和放射增强效应[1-3]。PARP1抑制剂INO-1001和ABT-888明显减少肌源性紧张度和改善内皮依赖性舒张，恢复内皮一氧化氮合酶磷酸化和cGMP，以及降低切割PARP1表达。PARP1抑制剂可能用来克服糖尿病微血管功能障碍[4]。

产品特性

1）   CAS NO：912444-00-9

2）   化学名：1-[3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one

3）   同义名：Veliparib free base; ABT-888; A-861695; NSC 737664;

4）   分子式：C13H16N4O

5）   分子量：244.29 g/mol

6）   纯度：>98%

7）   外观：白色至类白色结晶性固体或粉末

8）  溶解性：溶于DMSO（≥10mg/ml）【“>”：表明溶于标示浓度，但饱和溶解度未知。】

9）   化学结构式：

保存与运输方法

保存：-20ºC干燥保存，3年有效。

运输：常温运输。

注意事项

1）   为了让化合物更好的溶解，可通过37℃加热或（和）超声波水浴中震动片刻来处理。若实验所需浓度过大甚至达产品溶解极限，请添加助溶剂助溶或自行调整浓度。

2）   本品仅用作科研用途，不得用作临床诊断或治疗，不得用于食品或药品，绝对禁止用在人身上。

3）   为了您的安全和健康，请穿实验服并戴一次性手套操作。

储存液制备

质量         溶剂体积 浓度	1mg	5mg	10mg
1mM	4.0935 mL	20.4675 mL	40.9350 mL
5mM	0.8187 mL	4.0935 mL	8.1870 mL
10mM	0.4093 mL	2.0467 mL	4.0935 mL

使用方法【源自文献，仅作参考】

文献1，Boerner JL et al. Protein expression of DNA damage repair proteins dictates response to topoisomerase and PARP inhibitors in triple-negative breast cancer. PLoS One. 2015 Mar 16;10(3):e0119614.PMID: 25774912 体外研究（细胞实验）： 细胞类型（Cell type）：BRCA mutated TNBC cell lines: SUM149, SUM159 and SUM1315; HCC1937 and MDA-MB-231; MX-1; 药物配制（Preparation）：ABT-888 was dissolved in dimethylsulphoxide (DMSO) to make a stock concentration of 10mM and stored at -20°C. 实验方法（Assay）：Exponentially growing cells were seeded in 96-well plates (MX-1: 5,000 per well, all others: 2,000 per well) and the single agent drugs (ABT-888 or CPT-11) were addedin concentrations ranging from 0.01 nM to 100 μM the following day. When the drugs were used in combination, CPT-11 was added to media with a constant ABT-888 concentration of 500nM. Cell proliferation was determined 5 days after continuous exposure to drug by addition of MTT.

文献2，Liu X et al.Potentiation of Temozolomide Cytotoxicity by Poly(ADP)Ribose Polymerase Inhibitor ABT-888 Requires a Conversion of Single-Stranded DNA Damages to Double-Stranded DNA Breaks. Mol Cancer Res. 2008 Oct;6(10):1621-9. PMID: 18922977 体内研究（动物模型）： 动物模型（Animal Model）：B16F10 melanoma syngeneic model 药物配制（Preparation）：ABT-888 was delivered in a vehicle containing 0.9% NaCl adjusted to pH 4.0. 实验方法（Assay）：B16F10 cells (6×104) were injected s.c. into the flank of female C57BL/6 mice. Mice were injection-order allocated to treatment groups, and therapy was initiated on day 1 following inoculation. ABT-888 was delivered in a vehicle containing 0.9% NaCl adjusted to pH 4.0. Temozolomide was formulated using 0.2% hydroxypropyl methylcellulose.Temozolomide was administered on an oral, qd × 5 schedule on days 6 to 10 at 50 mg/kg/d concurrently with ABT-888 on an oral, bd × 5 schedule at 25, 5, and 1 mg/kg/d.The experiment consists of 10 mice per treatment group;

参考文献

[1] Donawho CK 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] Shelton JW et al. In vitro and in vivo enhancement of chemoradiation using the oral PARP inhibitor ABT-888 in colorectal cancer cells. Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):469-76.

[3] Shunkwiler L et al. Inhibition of Poly(ADP-Ribose) Polymerase Enhances Radiochemosensitivity in Cancers Proficient in DNA Double-Strand Break Repair. Int J Mol Sci. 2013 Feb 8;14(2):3773-85.

[4] Choi SK et al. Poly(ADP-ribose) polymerase 1 inhibition improves coronary arteriole function in type 2 diabetes mellitus. Hypertension. 2012 May;59(5):1060-8.