ASK1-IN-2

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ASK1-IN-2 是一种有效的口服活性凋亡信号调节激酶 1 (ASK1) 抑制剂，IC50 为 32.8 nM。 ASK1-IN-2 有可能用作溃疡性结肠炎的治疗策略。

ASK1-IN-2 is a potent and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with an IC50 of 32.8 nM. ASK1-IN-2 can potentially be used as a therapeutic strategy for ulcerative colitis.(In Vitro):ASK1-IN-2 displays potent anti-ASK1 kinase activity and strong inhibitory effect on ASK1 in AP1-HEK293 cells with inhibition rate of 95.59%.(In Vivo):ASK1-IN-2 (1 mg/kg; i.v.) shows low clearance (CL=1.38 L/h/kg) and moderate half-life (T1/2=1.45 h) in rats. ASK1-IN-2 (10 mg/kg; p.o.) shows high oral exposure (AUClast=4517 h?ng/mL), 62.2% oral bioavailability and acceptable terminal half-life (T1/2=2.31 h) in rats. ASK1-IN-2 (25 mg/kg; p.o. daily for 7 d) improves dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. ASK1-IN-2 (25 mg/kg; p.o. daily for 7 d) blocks ASK1-p38/JNK signaling pathways and reduces inflammatory cytokine levels in DSS-induced mouse colon tissues.

ASK1-IN-2 (compound 19) (10 mM; 1 h) inhibits the luciferase reporter activity in AP1-HEK293 cells, with inhibition rate of 95.59%.

ASK1-IN-2 (25 mg/kg; p.o. daily for 7 d) improves dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice.ASK1-IN-2 (25 mg/kg; p.o. daily for 7 d) blocks ASK1-p38/JNK signaling pathways and reduces inflammatory cytokine levels in DSS-induced mouse colon tissues.ASK1-IN-2 (1 mg/kg; i.v.) shows low clearance (CL=1.38 L/h/kg) and moderate half-life (T1/2=1.45 h) in rats.ASK1-IN-2 (10 mg/kg; p.o.) shows high oral exposure (AUClast=4517 h?ng/mL), 62.2% oral bioavailability and acceptable terminal half-life (T1/2=2.31 h) in rats. Animal Model:Male ICR mice (18-22 g, 6-8 weeks) were given 3% DSS (w/v) orally in drinking waterDosage:25 mg/kg Administration:P.o. daily for 7 days Result:Induced a significant recovery of body weight loss, with an increase of +11.2%.Decreased the disease activity index (DAI) score about a 2 unit.Significantly prevented colon shortening.Attenuated a severe colonic tissue damage and infiltration of inflammatory cells.Animal Model:Male SD rats Dosage:1 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) Administration:I.v. and p.o. administration Result:I.v.: CL=1.38 L/h/kg; T1/2=1.45 h.P.o.: AUClast=4517 h?ng/mL; F=62.2%; T1/2=2.31 h.

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Apoptosis

Apoptosis

PLK2|PLK3|PLK1

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2541792-70-3

364.38

C19H17FN6O

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (686.10 mM)

CC(C)n1c(-c2cccc(NC(c3cc(ccc(F)c4)c4[nH]3)=O)n2)nnc1

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(-20℃)

With Ice Pack

≥ 2 years