EC50: 0.2 μM for anti-HCV activity

RO8191 is an IFN-α receptor 2 agonist.

Most acute hepatitis C virus (HCV) infections become chronic and some progress to liver cirrhosis or hepatocellular carcinoma, with thes tandard therapy involving an interferon (IFN)-α-based regimen.

In vitro: Previous study found that RO8191had remarkable anti-HCV activity. More importantly, RO8191 exerted its antiviral activity by directly interacting with the type I IFN receptor to drive IFN-stimulated genes (ISG) expression, which then induced the antiviral response of innate immune system. Previous researchers conducted a systematic structure activity relationship (SAR) study on RO8191, and although more than 100 analogues were synthesized, none of the analogues displayed improved anti-HCV activity, suggesting that RO8191 displayed a relative narrow window of SAR [1].

In vivo: A previous study evaluated the effects of RO8191 on IFN signaling in mice. Results showd that the antiviral genes were significantly induced in the livers of mice treated with RO8191. In addition, genes that had previously been reported to be induced by IFN-b in mouse liver were also induced in the livers of RO8191-treated mice. This study also measured inflammatory cytokine and chemokine expressions, and RO8191 did not significantly induce the expression of these genes. To evaluate the in-vivo anti-HCV activity of RO8191, RO8191 was orally administered to HCV-infected humanized liver mice, and the results showed that RO8191 was able to reduce HCV titer in vivo [2].

Clinical trial: So far, no clinical study has been conducted.

References:
[1] Wang H, Wang S, Cheng L, Chen L, Wang Y, Qing J, Huang S, Wang Y, Lei X, Wu Y, Ma Z, Zhang L, Tang Y. Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor. ACS Med Chem Lett. 2015 Jul 27;6(9):977-81.
[2] Konishi H et al. An orally available, small-molecule interferon inhibits viral replication. Sci Rep. 2012;2:259.