Veliparib dihydrochloride
(Synonyms: 维利帕尼二盐酸盐; ABT-888 dihydrochloride) 目录号 : GC17783
An orally bioavailable inhibitor of PARP1 and PARP2
Cas No.:912445-05-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Veliparib dihydrochloride is a potent inhibitor of PARP-1 and PARP-2 with K (i) s of 5.2 and 2.9 nmol/L, respectively [1].
PARP is short of poly ADP ribose polymerase and is reported as an overexpressed enzyme in a variety of cancers. Since it has been revealed that several forms of cancer more independent on PARP compared with regular cells, which making PARP as an attractive target for cancer therapy. Many studies have shown that PARP inhibitors act as radio- and chemotherapy- sensitizers in preclinical studies using both in vitro and in vivo models [2] [3].
Veliparib dihydrochloride is a selective inhibitor of PARP. When tested with colon cancer cell lines HCT-116 and HT-29, using veliparib dihydrochloride as an adjuvant and combing with SN38 or Oxall resulted in increasing G2/M cell cycle arrest and increased levels of DNA damage via inhibiting PARP-1 and PARP-2 [4].
In mouse model with B16F10 murine melanoma cells injected subcutaneously, oral administration of veliparib dihydrochloride with temozolomide increased the efficacy at the concentration of 3.1 mg/kg/d~25 mg/kg/d and markedly slowed tumor progression. And similar results were achieved when tested with MX-1 breast xenograft model (BRCA1 deletion and BRCA2 mutation) or HCT-116 colon carcinoma model [1].
References:
[1]. Donawho, C.K., 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. 13(9): p. 2728-37.
[2]. Benafif, S. and M. Hall, An update on PARP inhibitors for the treatment of cancer. Onco Targets Ther, 2015. 8: p. 519-28.
[3]. Guillot, C., et al., PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models. BMC Cancer, 2014. 14: p. 603.
[4]. Davidson, D., et al., The PARP inhibitor ABT-888 synergizes irinotecan treatment of colon cancer cell lines. Invest New Drugs, 2013. 31(2): p. 461-8.
Kinase experiment: | PARP assays are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [3H]NAD+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter. |
Animal experiment: | For B16F10 syngeneic studies, 6×104 cells are mixed with 50% Matrigel and inoculated by s.c. injection into the flank of 6- to 8-week-old female C57BL/6 mice (20 g). For cisplatin efficacy studies, female nude mice are implanted s.c. by trocar with fragments (20-30 mm3) of human tumors harvested from s.c. grown tumors in nude mice hosts. For the carboplatin and MX-1 cyclophosphamide studies, female scid mice are inoculated with 200 μL of a 1:10 dilution of tumor brei in 45% Matrigel and 45% Spinner MEM. For these established tumor studies, tumors are allowed to grow to the indicated size and then randomized to therapy groups. For DOHH-2 xenograft studies, 1×106 cells are mixed with 50% Matrigel and inoculated by s.c. injection into the flank of male scid mice. Veliparib is delivered by either oral route or continuous infusion using s.c. placement of 14-day Alzet OMP model 2002 in a vehicle containing 0.9% NaCl adjusted to pH 4.0. The OMP delivers at a rate of 12 μL daily and Veliparib doses are calculated accordingly. Temozolomide, cisplatin, carboplatin, and cyclophosphamide are formulated according to the manufacturers' recommendations. |
References: [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. | |
| Cas No. | 912445-05-7 | SDF | |
| 别名 | 维利帕尼二盐酸盐; ABT-888 dihydrochloride | ||
| 化学名 | 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide;dihydrochloride | ||
| Canonical SMILES | CC1(CCCN1)C2=NC3=C(C=CC=C3N2)C(=O)N.Cl.Cl | ||
| 分子式 | C13H18Cl2N4O | 分子量 | 317.21 |
| 溶解度 | ≥ 31.7 mg/mL in DMSO, ≥ 3.3 mg/mL in EtOH with ultrasonic and warming, ≥ 104 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.1525 mL | 15.7624 mL | 31.5249 mL |
| 5 mM | 0.6305 mL | 3.1525 mL | 6.305 mL |
| 10 mM | 0.3152 mL | 1.5762 mL | 3.1525 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet