| Identification | Back Directory | [Name]
1(2H)-Phthalazinone, 4-[[3-[[5,6-dihydro-5-methyl-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]carbonyl]-4-fluorophenyl]methyl]- | [CAS]
1551355-46-4 | [Synonyms]
1(2H)-Phthalazinone, 4-[[3-[[5,6-dihydro-5-methyl-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]carbonyl]-4-fluorophenyl]methyl]- | [Molecular Formula]
C23H18F4N6O2 | [MOL File]
1551355-46-4.mol | [Molecular Weight]
486.42 |
| Chemical Properties | Back Directory | [density ]
1.56±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (205.58 mM; ultrasonic and warming and heat to 60°C) | [form ]
Solid | [pka]
12.06±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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.html" class="link-product" target="_blank">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[1]. | [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[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. |
| [IC 50]
PARP1: 0.74 nM (IC50); PARP2: 0.22 nM (IC50) | [storage]
Store at -20°C | [References]
[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. DOI:10.1016/j.canlet.2016.11.010 |
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