"目录号: HY-15233

Anti-infection-

Letermovir 是一种新颖的CMV抑制剂，以病毒末端酶为靶目标，抑制其活性。

CMV

相关产品

Maribavir-Cidofovir-CMX001-Brivudine-Valganciclovir hydrochloride-

生物活性

Description

Letermovir is a novel inhibitor ofCMV, which targets the viral terminase complex and remains active against virus resistant to DNA polymerase inhibitors.

In Vitro

AIC246 has consistent antiviral efficacy, and there is remarkable selectivity of AIC246 for human cytomegaloviruses[1]. AD169 mutant strains and designated rAIC246-1 and rAIC246-2 are highly resistant to Letermovir (AIC246), with EC50s of 5.6 nM, 1.24 μM, 0.37 μM, respectively. Letermovir inhibits HCMV replication through a specific antiviral mechanism that involves the viral gene product UL56. Letermovir inhibits HCMV replication in cell culture by interfering with the proper cleavage/packaging of HCMV progeny DNA[2]. Letermovir inhibits the current gold standard GCV by more than 400-fold with respect to EC50s (mean, 4.5 nM versus 2 μM) and by more than 2,000-fold with respect to EC90values (mean, 6.1 nM versus 14.5 μM)[3]. Letermovir in conbination with anti-HCMV drugs causes additive antiviral effects, but there is no interaction between letermovir and anti-HIV drugs[4].

In Vivo

Letermovir (10-100 mg/kg/day, p.o.) leads to a dose-dependent reduction of the HCMV titer in transplanted cells compared to that of the placebo-treated control group using the mouse xenograft model[3].

Clinical Trial

NCT01063829

AiCuris Anti-infective Cures GmbH-Quintiles, Inc.

Cytomegalovirus

February 2010

Phase 2

NCT01063829

AiCuris Anti-infective Cures GmbH-Quintiles, Inc.

Cytomegalovirus

February 2010

Phase 2

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References

[1].Marschall M, et al. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother. 2012 Feb;56(2):1135-7.

[2].Goldner T, et al. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93.

[3].Lischka P, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010 Mar;54(3):1290-7.

[4].Wildum S, et al. In vitro drug combination studies of?Letermovir?(AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication. Antimicrob Agents Chemother. 2015;59(6):3140-8.