CHIKV-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

CHIKV-IN-2 显示出针对细胞靶标二氢乳清酸脱氢酶 (DHODH) 的抑制活性，该酶与多种病毒相互作用，并通过消耗细胞内嘧啶池来调节病毒的复制。

CHIKV-IN-2 shows inhibitory activity against a cellular target Dihydroorotate Dehydrogenase (DHODH), which interacts with various viruses and regulate their replication via depleting intracellular pyrimidine pools. Therefore, CHIKV-IN-2 is a potent inhibitor against Chikungunya virus (CHIKV), with excellent cellular antiviral activity (EC90=270 nM) and improved liver microsomal stability.(In Vitro):CHIKV-IN-2 is active against alphavirus VEEV (EC90=0.40 μM) as well as flaviviruses such as West Nile Virus (WNV, EC90=0.20 μM) and Dengue Virus Strain-2 (DENV-2, EC90=0.60 μM). CHIKV-IN-2 is a potent pan-alphavirus inhibitor, with EC90s of 0.85-2.5 μM for CHIKV clinical isolates and attenuated vaccine strains.(In Vivo):CHIKV-IN-2 (40 mg/kg; p.o., i.p., s.c.) exhibits moderate bioavailability (F=41%, 43%, 4%), terminal elimination half-life (t1/2=9.9, 18.5, 18.6 h) and Cmax (642, 858, 90 ng/mL) in mice. CHIKV-IN-2 (80 mg/kg; i.p. twice a day for 3 days) significantly decreases infectious CHIKV dissemination to other tissues of mice. CHIKV-IN-2 (1 mg/kg; i.v.) exhibits terminal elimination half-life (t1/2= 2.02 h) and AUC (497 h?ng/mL) in mice.

CHIKV-IN-2 (compound 8q) is a potent pan-alphavirus inhibitor, with EC90s of 0.85-2.5 μM for CHIKV clinical isolates and attenuated vaccine strains.CHIKV-IN-2 is active against alphavirus VEEV (EC90=0.40 μM) as well as flaviviruses such as West Nile Virus (WNV, EC90=0.20 μM) and Dengue Virus Strain-2 (DENV-2, EC90=0.60 μM).

CHIKV-IN-2 (compound 8q) (80 mg/kg; i.p. twice a day for 3 days) significantly decreases infectious CHIKV dissemination to other tissues of mice.CHIKV-IN-2 (40 mg/kg; p.o., i.p., s.c.) exhibits moderate bioavailability (F=41%, 43%, 4%), terminal elimination half-life (t1/2=9.9, 18.5, 18.6 h) and Cmax (642, 858, 90 ng/mL) in mice.CHIKV-IN-2 (1 mg/kg; i.v.) exhibits terminal elimination half-life (t1/2= 2.02 h) and AUC (497 h?ng/mL) in mice. Animal Model:Female and male C57BL/6 mice Dosage:80 mg/kg Administration:I.p. twice a day for 3 days Result:Failed to inhibit virus loads at the site of infection.Decreased virus dissemination to other tissues.Animal Model:Male C57BL/6 mice were challenged with CHIKV in the right footpad Dosage:1 mg/kg for i.v. and 40 mg/kg for p.o., i.p., s.c. (Pharmacokinetic Analysis)Administration:I.v., p.o., i.p., s.c.Result:I.v.: t1/2= 2.02 h; AUC=497 h?ng/mL.

——

Metabolic Enzyme/Protease

Dehydrogenase

NAE

——

——

2361289-44-1

362.46

C23H26N2O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (275.89 mM)

CC(C)(c(cc1)ccc1NC(c(cc(CCCCC1)c1c1)c1OC)=O)C#N

——

(-20℃)

With Ice Pack

≥ 2 years