吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼

简介生物活性靶点体外研究体内研究吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼试剂级价格

CAS号:895158-95-9
英文名:SC 144
中文名:吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼
CBNumber:CB72666896
分子式:C16H11FN6O
分子量:322.3
MOL File:895158-95-9.mol

吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼化学性质

密度 :1.53±0.1 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :insoluble in EtOH; insoluble in H2O; ≥16.1 mg/mL in DMSO
形态 :solid
酸度系数(pKa) :8.87±0.43(Predicted)

吡嗪羧酸 2-(7-氟吡咯并[1,2-A]喹喔啉-4-基)酰肼性质、用途与生产工艺

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

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.

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%.