Simmiparib|cas:1551355-46-4|西域试剂

Simmiparib,99.51%

产品编号：Bellancom-115552| CAS NO：1551355-46-4| 分子式：C₂₃H₁₈F₄N₆O₂| 分子量：486.42

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货号	价格	库存与货期
Bellancom-115552	￥3500.00	杭州北京（现货）
Bellancom-115552	￥5800.00	杭州北京（现货）
Bellancom-115552	￥11000.00	杭州北京（现货）

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Simmiparib

产品介绍

Simmiparib 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 (HY-10162)。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。

生物活性

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 (HY-10162). 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.

体外研究

Simmiparib (0-10 μM; 3 days) exhibits anti-proliferative activity against various cancer cells.
Simmiparib (0-10 μM; 48 h) induces typical G2/M arrest in Capan-1 cells.
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.
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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

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

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

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

Cell Line:	V-C8 (BRCA2^-/-)
Concentration:	0.5 and 2 μM
Incubation Time:	24 h
Result:	Caused more than 57% apoptosis.

Western Blot Analysis

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.

体内研究
(In Vivo)

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.
Simmiparib (10 and 50 mg/kg; p.o.; qd, for 42 days) inhibits the growth of BRCA1-mutated breast cancer in xenograft mice model.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/cA nude mice (Subcutaneously injected with BRCA2^-/- V-C8 cells and BRCA2^-/- MDA-MB-436 cells)
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)
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/cA nude mice (Subcutaneously injected with BRCA2^-/- V-C8 cells and BRCA2^-/- MDA-MB-436 cells)
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)
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/cA nude mice (Subcutaneously injected with BRCA2^-/- V-C8 cells and BRCA2^-/- MDA-MB-436 cells)
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)
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.

性状

Solid

溶解性数据

In Vitro:

DMSO : 100 mg/mL (205.58 mM; ultrasonic and warming and heat to 60°C)

配制储备液

浓度溶剂体积质量	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

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, 6 months; -20°C, 1 month。-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。

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式