吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼
中文名称:
吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼
中文同义词:
吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼;GP130抑制剂(SC144);2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)吡嗪羧酸酰肼
英文名称:
SC 144
英文同义词:
2-Pyrazinecarboxylic acid, 2-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)hydrazide;2-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)hydrazide;SC 144;SC144;SC-144;Pyrazinecarboxylic acid 2-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)hydrazide;SC 144; SC144;CS-805
CAS号:
895158-95-9
分子式:
C16H11FN6O
分子量:
322.3
EINECS号:
相关类别:
小分子抑制剂，天然产物;细胞生物学试剂;Inhibitors
Mol文件:
895158-95-9.mol
密度
1.53±0.1 g/cm3(Predicted)
酸度系数(pKa)
8.87±0.43(Predicted)
简介
SC144是一种口服活性小分子gp130抑制剂。
生物活性
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。
靶点
IL6-beta
IL6-beta
体外研究
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).
The potency of SC144 toward NCI/ADR-RES (Paclitaxel- and Doxorubicin-resistant, IC 50 =0.43 μM) and HEY (Cisplatin-resistant, IC 50 =0.88 μM) suggests an ability to overcome drug resistance in ovarian cancer.
SC144 (2 μM; 24 hours) causes significantly more apoptosis in OVCAR-8 and Caov-3 than normal kidney epithelial and normal endometrial cells.
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.
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.
Apoptosis Analysis
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
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.
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.
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
SC144 (10 mg/kg; i.p.; daily for 58 days) suppresses tumor growth in human ovariancancer xenografts.
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.
Animal Model: Athymic mice (human ovarian cancer xenograft)
Dosage: 10 mg/kg
Administration: I.p; daily for 58 days
Result: Significantly inhibited tumor growth by about 73%.
Animal Model:
Athymic mice (human ovarian cancer xenograft)
Dosage:
10 mg/kg
Administration:
I.p; daily for 58 days
Result:
Significantly inhibited tumor growth by about 73%.
