| Description | IDX184 is a potent, orally active, targeted HCV polymerase inhibitor and nucleoside polymerase.IDX184 effectively inhibits HCV polymerase (IC50=0.31 μM, Ki=52.3 nM). IDX184 is a liver-targeted nucleotide prodrug with anti-HCV activity that inhibits HCV NS5B polymerase and can be used in combination with pegylated interferon-α2a and ribavirin for the primary treatment of chronic hepatitis C. It has been shown to inhibit HCV polymerase and nucleoside polymerase. |
| In vitro | IDX184, a liver-targeted prodrug of the nucleotide 2′-MeG-MP, serves as a hepatitis C virus polymerase inhibitor with liver-specific targeting.[1]IDX184 is not toxic (CC50>100μM) in any tested cell line.[2]IDX184 is a second-generation, orally bioavailable nucleotide prodrug designed to provide increased anti-HCV efficacy and safety versus the parent nucleoside. In HCV replicon testing, IDX184 is the most potent inhibitor (EC50=0.3-0.45 μM) compared to any of the 2’ or 4’ modified nucleosides (EC50=4-6 μM) and is also highly inhibitory in the JFH-1 infectious system (EC50=0.06-0.11 μM).[2] |
| Target activity | HCV polymerase:0.31 μM (IC50), HCV polymerase:52.3 nM (Ki) |
| Synonyms | IDX-184, IDX 184 |
| molecular weight | 626.62 |
| Molecular formula | C25H35N6O9PS |
| CAS | 1036915-08-8 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 50 mg/mL (79.79 mM) |
| References | 1. Elfiky AA. Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials. J Med Virol. 2016 Dec;88(12):2044-2051. doi: 10.1002/jmv.24678. PubMed PMID: 27604059. 2. Gentile I, Buonomo AR, Zappulo E, Borgia G. Discontinued drugs in 2012 - 2013: hepatitis C virus infection. Expert Opin Investig Drugs. 2015 Feb;24(2):239-51. doi: 10.1517/13543784.2015.982274. PubMed PMID: 25384989. 3. Elfiky AA, Mahdy SM, Elshemey WM. Quantitative structure-activity relationship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses. J Med Virol. 2016 Nov 19. doi: 10.1002/jmv.24736. [Epub ahead of print] PubMed PMID: 27864902. 4. Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Zennou V, Otto MJ, Furman PA. Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA. J Virol. 2011 Dec;85(23):12334-42. doi: 10.1128/JVI.05639-11. PubMed PMID: 21957306; PubMed Central PMCID: PMC3209386. |