molecules of the month

AL-611 is a prodrug to a nucleoside inhibitor of HCV NS5B polymerase. While there have been very successful nucleoside drugs (e.g. sofosbuvir), several nucleoside inhibitors of HCV previously failed in the clinic due to severe toxicities, in some cases due to incorporation of the nucleosides into host RNA. The Janssen Biopharma (formerly Alios) team tried to navigate safety issues observed with other nucleosides by increasing the complexity of the sugar moiety. The presence of two fully-substituted, fluorine-bearing stereogenic carbons caught my eye. AL-611 is orally available in dogs and was selected as a drug candidate but discontinued due to the effectiveness of already approved drugs.