Simmiparib
Based on 1 Customer Validation
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.
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- Pureza: 99.01%
- No. CAS: 1551355-46-4
- Fòrmula: C23H18F4N6O2
- Peso molecular:486.42
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
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PARP1 0.74 nM (IC50) |
PARP2 0.22 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-436 | IC50 |
1.3 nM
Compound: 9
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Antiproliferative activity against human MDA-MB-436 BRCA1-/- cells assessed as inhibition of cell growth incubated for 7 days by CCK-8 assay
Antiproliferative activity against human MDA-MB-436 BRCA1-/- cells assessed as inhibition of cell growth incubated for 7 days by CCK-8 assay
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[PMID: 37567056] |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Various cancer cells harboring deficient BRCA1, BRCA2, PTEN and EWS-FLI1
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Concentration:0-10 μM
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Incubation Time:3 days
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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.
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Cell Line:Capan-1 cells
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Concentration:0, 1, 3 and 10 μM
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Incubation Time:48 h
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Result:Induced typical G2/M arrest in a concentration-dependent manner.
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Cell Line:MDA-MB-436
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Concentration:0.1 and 1 μM
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Incubation Time:24 h
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Result:Led to 39.64% and 42.98% apoptosis at 0.1 and 1 μM, respectively.
Increased dose-dependently the levels of γH2AX.
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Cell Line:V-C8 (BRCA2-/-)
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Concentration:0.5 and 2 μM
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Incubation Time:24 h
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Result:Caused more than 57% apoptosis.
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Cell Line:Capan-1
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Concentration:1 and 10 μM
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Incubation Time:48 h or 72 h
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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 (10 and 50 mg/kg; p.o.; qd, for 42 days) inhibits the growth of BRCA1-mutated breast cancer in xenograft mice model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/cA nude mice (Subcutaneously injected with BRCA2-/- V-C8 cells and BRCA2-/- MDA-MB-436 cells)[1]
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Dosage:2, 4 and 8 mg/kg
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Administration:p.o.; qd, for 14 days
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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.
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Animal Model:Female BALB/cA nude mice (Subcutaneously injected with cancer cells derived from BRCA1-mutated BR-05-0028 breast cancer tissue)[1]
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Dosage:10 and 50 mg/kg
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Administration:p.o.; qd, for 42 days
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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.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 1551355-46-4
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Appearance Solid
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Peso molecular 486.42
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Fòrmula C23H18F4N6O2
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Color White to off-white
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SMILES
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
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (205.58 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (280 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0558 mL | 10.2792 mL | 20.5584 mL | 51.3959 mL |
| 5 mM | 0.4112 mL | 2.0558 mL | 4.1117 mL | 10.2792 mL | |
| 10 mM | 0.2056 mL | 1.0279 mL | 2.0558 mL | 5.1396 mL | |
| 15 mM | 0.1371 mL | 0.6853 mL | 1.3706 mL | 3.4264 mL | |
| 20 mM | 0.1028 mL | 0.5140 mL | 1.0279 mL | 2.5698 mL | |
| 25 mM | 0.0822 mL | 0.4112 mL | 0.8223 mL | 2.0558 mL | |
| 30 mM | 0.0685 mL | 0.3426 mL | 0.6853 mL | 1.7132 mL | |
| 40 mM | 0.0514 mL | 0.2570 mL | 0.5140 mL | 1.2849 mL | |
| 50 mM | 0.0411 mL | 0.2056 mL | 0.4112 mL | 1.0279 mL | |
| 60 mM | 0.0343 mL | 0.1713 mL | 0.3426 mL | 0.8566 mL | |
| 80 mM | 0.0257 mL | 0.1285 mL | 0.2570 mL | 0.6424 mL | |
| 100 mM | 0.0206 mL | 0.1028 mL | 0.2056 mL | 0.5140 mL |
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