Simmiparib - ≥99% , CAS No.1551355-46-4

CAS: 1551355-46-4 Cat. No.: S650119 分子式: C₂₃H₁₈F₄N₆O₂ 分子量: 486.42

GRADE & PURITY ≥99%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

概要

Simmiparib is a highly potent and orally active PARP1 and PARP2 inhibitor with IC 50 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

In Vitro

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell 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 IC 50 s of 0.2 nM, 4.6 nM, 20 nM, 21 nM and 36 nM, respectively. Cell Cycle AnalysisCell 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 AnalysisCell 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 AnalysisCell Line: V-C8 (BRCA2 -/- ) Concentration: 0.5 and 2 μM Incubation Time: 24 h Result: Caused more than 57% apoptosis. Western Blot AnalysisCell 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.

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 . MCE 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.

Form:Solid

IC50& Target:PARP1 0.74 nM (IC 50 ) PARP2 0.22 nM (IC 50 )

Specifications

仕様と純度

≥99%

生化学的・生理学的メカニズム

Simmiparib is a highly potent and orally active PARP1 and PARP2 inhibitor with IC 50 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 bre

保管条件

Store at -20°C

入荷

Ice chest + Ice pads

この製品は冷冷この冷このこの製品の運送が必要です。地上およびその他の経済サービスは利用できません。

純度

≥99%

名前と識別子

• カノニカル・スマイル: O=C1NN=C(CC2=CC=C(F)C(C(N3CC4=NN=C(C(F)(F)F)N4C(C)C3)=O)=C2)C5=C1C=CC=C5
• 分子量: 486.42

化学的性質と物理的性質

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

よくある質問

What is the purity of this product?

This product is supplied at ≥99% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1551355-46-4, the molecular formula is C23H18F4N6O2, and the molecular weight is 486.42 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.