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，进而抑制下游靶基因的表达。SC144 hydrochloride 对 gp130 配体触发的信号转导显示有效的抑制作用。SC144 hydrochloride 诱导人卵巢癌细胞凋亡。

SC144 hydrochloride is a first-in-class, orally active small-molecule gp130 (IL6-beta) inhibitor. SC144 hydrochloride binds gp130, induces gp130 phosphorylation (S782) and deglycosylation, abrogates Stat3 phosphorylation and nuclear translocation, and further inhibits the expression of downstream target genes. In addition, SC144 hydrochloride shows potent inhibition of gp130 ligand-triggered signaling. SC144 hydrochloride induces apoptosis in human ovarian cancer cells [1].

SC144 inhibits cell growth in a panel of human ovarian cancer cell lines with IC 50 s in a submicromolar range (IC 50 =OVCAR-8, OVCAR-5, OVCAR-3= 0.72, 0.49, 0.95 μM) [1]. The potency of SC144 against NCI/ADR-RES (Paclitaxel- and Doxorubicin-resistant, IC 50 =0.43 μM) and HEY (Cisplatin-resistant, IC 50 =0.88 μM) demonstrates 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.

SC144 (10 mg/kg; i.p.; daily for 58 days) delays 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%.

917497-70-2

C16H12ClFN6O

358.76

SC144 hydrochloride

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years