SC144 是首创的口服活性gp130 (IL6-beta)抑制剂。SC144 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 对 gp130 配体触发的信号转导有明显的抑制作用。SC144 诱导人卵巢癌细胞凋亡。
| 生物活性 | SC144 is a first-in-class, orally activegp130 (IL6-beta)inhibitor. SC144 binds gp130, induces gp130 phosphorylation (S782) and deglycosylation, abrogatesStat3phosphorylation and nuclear translocation, and further inhibits the expression of downstream target genes. SC144 shows potent inhibition of gp130 ligand-triggered signaling. SC144 inducesapoptosisin human ovariancancercells[1]. |
| IC50& Target[1] | |
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. |
|
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: | 10 mg/kg | | Administration: | I.p; daily for 58 days | | Result: | Significantly inhibited tumor growth by about 73%. |
|
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 溶解性数据 | In Vitro: DMSO : 16.67 mg/mL(51.72 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1027 mL | 15.5135 mL | 31.0270 mL | | 5 mM | 0.6205 mL | 3.1027 mL | 6.2054 mL | | 10 mM | 0.3103 mL | 1.5513 mL | 3.1027 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。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
