“compound 9” is an investigational prodrug of pibrentasvir (ABT-530), a key component of AbbVie’s marketed HCV combination Mavyret. Pibrentasvir (PIB) is the largest approved oral small molecule since 1983 (MW = 1113, not including the peptide semaglutide at MW = 4113), and came with some solubility issues (aq. sol. pH 7 = <0.0001 mg/mL). The [...]

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 [...]

The Janssen pan-genotype, pan-serotype dengue virus inhibitor, JNJ-A07 , demonstrates broad activity against a panel of 21 clinical isolates and has a high barrier to resistance. It blocks the interaction between the non-enzymatic NS4B protein and NS3, preventing them from forming an NS3-NS4B complex which is essential for replication (though [...]

GSK2818713 is an HCV NS5A replication complex inhibitor with an interesting biphenylene linker. The crowded, hotly competitive NS5A space has led to a lot of creative chemical scaffolds including this one.

AM-2-19 (SF001) is an analog of the notoriously toxic IV antifungal drug, amphotericin B (AmB). Compared with AmB, AM-2-19 is significantly less toxic against primary human cells and in mice, while more broadly active against fungal pathogens including antifungal drug-resistant strains. SF001 received Fast-Track Designation from the FDA in 2023 and has progressed to Ph. I clinical development. This article highlights the history of antifungal polyene natural products, a new mechanistic hypothesis for polyene antibiotic activity, and the design of 3rd generation Erg-specific polyenes.