SC144 hydrochloride 是首创的口服活性gp130 (IL6-beta)抑制剂。SC144 hydrochloride 结合 gp130，诱导 gp130 磷酸化(S782) 和去糖基化，消除 Stat3 磷酸化和核易位，进一步抑制下游靶基因的表达。SC144 hydrochloride 对 gp130 配体触发的信号转导有明显的抑制作用。SC144 hydrochloride 诱导人卵巢癌细胞凋亡。
| 生物活性 | SC144 hydrochloride is a first-in-class, orally activegp130 (IL6-beta)inhibitor. SC144 hydrochloride binds gp130, induces gp130 phosphorylation (S782) and deglycosylation, abrogatesStat3phosphorylation and nuclear translocation, and further inhibits the expression of downstream target genes. SC144 hydrochloride shows potent inhibition of gp130 ligand-triggered signaling. SC144 hydrochloride inducesapoptosisin human ovariancancercells[1]. |
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体外研究
(In Vitro) | SC144 inhibits cell growth in a panel of human ovarian cancer cell lines with IC50s in a submicromolar range (IC50=OVCAR-8, OVCAR-5, OVCAR-3= 0.72, 0.49, 0.95 μM)[1].
The potency of SC144 toward NCI/ADR-RES (Paclitaxel- and Doxorubicin-resistant, IC50=0.43 μM) and HEY (Cisplatin-resistant, IC50=0.88 μM) suggests an ability to overcome drug resistance in ovarian cancer[1].
SC144 (2 μM; 24 hours) causes significantly more apoptosis in OVCAR-8 and Caov-3 than normal kidney epithelial and normal endometrial cells[1].
SC144 (0.5-2 μM; 0-6 hours) substantially increases the phosphorylation of gp130 (S782) in both OVCAR-8 and Caov-3 cells in a time- and dose-dependent manner[1].
SC144 is cytotoxic to ovarian cancer cells via a mechanism involving the inhibition of gp130 activity, leading to the inactivation of Akt and Stat3 as well as the suppression of Stat3-regulated gene expression. As are result, SC144 treatment eventually causes cell-cycle arrest, anti-angiogenesis, and apoptosis[1].
Apoptosis Analysis[1] | Cell Line: | OVCAR-8 and Caov-3 cells | | Concentration: | 2 μM | | Incubation Time: | 24 hours | | Result: | Significantly caused cell death in OVCAR-8 and Caov-3 cells. |
Western Blot Analysis[1] | Cell Line: | OVCAR-8, Caov-3 cells | | Concentration: | 0.5-2 μM | | Incubation Time: | 0-6 hours | | Result: | Substantially increased the phosphorylation of gp130 (S782) in both OVCAR-8 and Caov-3 cellsin a time- and dose-dependent manner. |
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体内研究
(In Vivo) | SC144 (10 mg/kg; i.p.; daily for 58 days) suppresses tumor growth in human ovariancancer xenografts[1].
SC144 (100 mg/kg; p.o.; daily for 35 days) treatment shows the average tumor volume in mice 82% smaller than that in the control group[1].
| Animal Model: | Athymic mice (human ovarian cancer xenograft)[1] | | Dosage: | I.p; daily for 58 days | | Administration: | 10 mg/kg | | Result: | Significantly inhibited tumor growth by about 73%. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 10 mg/mL(27.87 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 | 1 mM | 2.7874 mL | 13.9369 mL | 27.8738 mL | | 5 mM | 0.5575 mL | 2.7874 mL | 5.5748 mL | | 10 mM | 0.2787 mL | 1.3937 mL | 2.7874 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 1 mg/mL (2.79 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.79 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*以上所有助溶剂都可在本网站选购。 |
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