Simmiparib
目录号 : GC67962Simmiparib 是一种高效且具有口服活性的 PARP1 和 PARP2 抑制剂，IC50 分别为 1.75 nM 和 0.22 nM。Simmiparib 对 PARP1/2 的抑制作用强于其母体化合物 Olaparib 。在同源重组修复 (HR) 缺陷细胞中，Simmiparib 诱导 DNA 双链断裂 (DSB) 积累和 G2/M 阻滞，从而诱导细胞凋亡 (apoptosis)。Simmiparib 在细胞和裸鼠移植瘤模型中都表现出显著的抗癌活性。
Cas No.:1551355-46-4
Sample solution is provided at 25 µL, 10mM.
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Simmiparib is a highly potent and orally active PARP1 and PARP2 inhibitor with IC50 values of 1.75 nM and 0.22 nM, respectively. Simmiparib has more potent PARP1/2 inhibition than its parent Olaparib . Simmiparib induces DNA double-strand breaks (DSB) accumulation and G2/M arrest in homologous recombination repair (HR)-deficient cells, thereby inducing apoptosis. Simmiparib exhibits remarkable anticancer activities in cells and nude mice bearing xenografts[1].
Simmiparib (0-10 μM; 3 days) exhibits anti-proliferative activity against various cancer cells[1].
Simmiparib (0-10 μM; 48 h) induces typical G2/M arrest in Capan-1 cells[1].
Simmiparib (0.1-2 μM; 24 h) induces apoptosis in MDA-MB-436 and V-C8 (BRCA2-/-) cells, and increases dose-dependently the levels of γH2AX[1].
Simmiparib (1-10 μM; 48 h or 72 h) increases the phosphorylation levels of Chk1 and Chk2 and the protein levels of p-Cyclin B1 (S147), Cyclin B1, p-CDK1 (Y15) and CDK1[1].
Cell Proliferation Assay[1]
| Cell Line: | Various cancer cells harboring deficient BRCA1, BRCA2, PTEN and EWS-FLI1 |
| Concentration: | 0-10 μM |
| Incubation Time: | 3 days |
| Result: | Exhibited anti-proliferative activity against MDA-MB-436 (BRCA1-/-), RD-ES (EWS-FLI1), DoTc2-4510 (BRCA2-/-), Capan-1 (BRCA2-/-) and U251 (PTEN-/-) with IC50s of 0.2 nM, 4.6 nM, 20 nM, 21 nM and 36 nM, respectively. |
Cell Cycle Analysis[1]
| Cell Line: | Capan-1 cells |
| Concentration: | 0, 1, 3 and 10 μM |
| Incubation Time: | 48 h |
| Result: | Induced typical G2/M arrest in a concentration-dependent manner. |
Apoptosis Analysis[1]
| Cell Line: | MDA-MB-436 |
| Concentration: | 0.1 and 1 μM |
| Incubation Time: | 24 h |
| Result: | Led to 39.64% and 42.98% apoptosis at 0.1 and 1 μM, respectively. Increased dose-dependently the levels of γH2AX. |
Apoptosis Analysis[1]
| Cell Line: | V-C8 (BRCA2-/-) |
| Concentration: | 0.5 and 2 μM |
| Incubation Time: | 24 h |
| Result: | Caused more than 57% apoptosis. |
Western Blot Analysis[1]
| Cell Line: | Capan-1 |
| Concentration: | 1 and 10 μM |
| Incubation Time: | 48 h or 72 h |
| Result: | Increased the phosphorylation levels of Chk1 and Chk2 but did not change the levels of the corresponding total proteins. Increased the protein levels of p-Cyclin B1 (S147), Cyclin B1, p-CDK1 (Y15) and CDK1. |
Simmiparib (2, 4 and 8 mg/kg; p.o.; qd, for 14 days) inhibits the growth of tumor in V-C8 (BRCA2-/-) and MDA-MB-436 (BRCA2-/-) xenograft mice models[1].
Simmiparib (10 and 50 mg/kg; p.o.; qd, for 42 days) inhibits the growth of BRCA1-mutated breast cancer in xenograft mice model[1].
| Animal Model: | Female BALB/cA nude mice (Subcutaneously injected with BRCA2-/- V-C8 cells and BRCA2-/- MDA-MB-436 cells)[1] |
| Dosage: | 2, 4 and 8 mg/kg |
| Administration: | p.o.; qd, for 14 days |
| Result: | Apparently inhibited the growth of the V-C8 tumor with an inhibition rate of 74.53% at 8 mg/kg. Suppressed the growth of the BRCA1-deficient MDA-MB-436 xenografts in a dose-dependent manner with its average inhibition rates of 64.93, 82.98 and 85.79% at 2, 4 and 8 mg/kg. Did not cause significant loss of body weight. |
| Animal Model: | Female BALB/cA nude mice (Subcutaneously injected with cancer cells derived from BRCA1-mutated BR-05-0028 breast cancer tissue)[1] |
| Dosage: | 10 and 50 mg/kg |
| Administration: | p.o.; qd, for 42 days |
| Result: | Elicited dose-dependent growth inhibition with the inhibition rate of 76.73% and 93.82% at 10 mg/kg and 50 mg/kg, respectively. |
[1]. Yuan B, et al. Poly(ADP-ribose)polymerase (PARP) inhibition and anticancer activity of simmiparib, a new inhibitor undergoing clinical trials. Cancer Lett. 2017 Feb 1;386:47-56.
| Cas No. | 1551355-46-4 | SDF | Download SDF |
| 分子式 | C23H18F4N6O2 | 分子量 | 486.42 |
| 溶解度 | DMSO : 100 mg/mL (205.58 mM; ultrasonic and warming and heat to 60°C) | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0558 mL | 10.2792 mL | 20.5584 mL |
| 5 mM | 0.4112 mL | 2.0558 mL | 4.1117 mL |
| 10 mM | 0.2056 mL | 1.0279 mL | 2.0558 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet