| CAS NO: | 895158-95-9 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
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| 5mg | 询价 |
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| 25mg | 询价 |
| 50mg | 询价 |
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| Molecular Weight (MW) | 322.3 |
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| Formula | C16H11FN6O |
| CAS No. | 895158-95-9 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 28 mg/mL (86.8 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | 30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL |
| Synonyms | SC-144; SC144; SC 144; Chemical Name: 2-Pyrazinecarboxylic Acid 2-(7-Fluoropyrrolo[1,2-a]quinoxalin-4-yl)hydrazide SMILES Code: O=C(C1=NC=CN=C1)NNC2=NC3=C(N4C2=CC=C4)C=CC(F)=C3 |
| In Vitro | In vitro activity: SC144 exhibits potent cytotoxicity against a panel of drug-sensitive and drug-resistant cancer cell lines. SC144 shows synergism with both 5-fluorouracil and oxaliplatin when co-treated in colorectal cancer HT29 cells. Pretreatment with SC144 in oxaliplatin-resistant HTOXAR3 cells is more effective than oxaliplatin pretreatment. In addition, the combination of SC144 and paclitaxel exhibited synergism in MDA-MB-435 cells with a schedule-dependent block in cell cycle. SC144 treatment in vitro induces gp130 phosphorylation and deglycosylation, resulting in the downregulation of surface-bound gp130 and the abrogation of gp130-associated Stat3 activation. In addition, SC144 selectively inhibits the downstream signaling activation induced by gp130 substrates, including IL-6 and LIF. Protein expression regulated by the gp130/Stat3 axis in OVCAR-8 cells is also down-regulated after SC144 treatment, including Bcl-2, Bcl-XL, survivin, cyclin D1, MMP-7, gp130 and Ape1/Rel-1. Kinase Assay: OVCAR-8 cells were lysed using M-PER supplemented with protease and phosphatase inhibitors. The supernatant of cell lysate containing 4 to 6 μg/μL total proteins was incubated with SC144 at indicated concentrations (0, 1, 10, 100, 1000 μmol/L) at room temperature for 1 hr, followed by proteolysis with 1 μg pronase to every 9,600 μg of lysate for 30 mins at room temperature. Final concentration of DMSO was 1% in all samples. To stop proteolysis, 5 × SDS sample loading buffer [Tris-HCl 0.25 mol/L, pH 6.8, SDS 10%, glycerol 50%, bromophenol blue 0.5%, dithiothreitol (DTT) 100 mmol/L] was added to each sample at a 1:4 ratio, mixed well, and boiled at 100℃ for 5 mins. Samples were analyzed by Western blotting. Cell Assay: SC144 treatment in vitro induced gp130 phosphorylation and deglycosylation, resulting in the downregulation of surface-bound gp130 and the abrogation of gp130-associated Stat3 activation. In addition, SC144 selectively inhibited the downstream signaling activation induced by gp130 substrates, including IL-6 and LIF. In OVCAR-8 cells, protein expression regulated by the gp130/Stat3 axis was also down-regulated after SC144 treatment, including Bcl-2, Bcl-XL, survivin, cyclin D1, MMP-7, gp130 and Ape1/Rel-1. |
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| In Vivo | SC144 significantly inhibits tumor growth in a mouse xenograft model of human ovarian cancer via i.p. or p.o. administration. After SC144 treatment for two months, gp130, Bcl-2, Bcl-XL, MMP-7 and Ape1/Ref-1 protein levels are substantially decreased in the tumor site in the treatment group compared with the control group. In an MDA-MB-435 mouse xenograft model, co-administration of SC144 and paclitaxel delays tumor growth in an SC144 dose-dependent manner. Evaluation of the pharmacokinetics of SC144 reveals that intraperitoneal administration of SC144 shows a two-compartmental pharmacokinetics elimination profile that is not observed in the oral dosing. |
| Animal model | Human Ovarian Cancer OVCAR-8 Xenograft |
| Formulation & Dosage | Formulated in 0.9% NaCl with 40% propylene glycol; 10 mg/kg daily; i.p. or p.o. |
| References | Anticancer Drugs. 2009 Jun;20(5):312-20; Mol Cancer Ther. 2013 Jun;12(6):937-49; Cancer Lett. 2013 Jul 28;335(2):421-30. |
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