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.