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.

INE963 (Novartis Institute for Tropical Diseases) is an oral, single dose, fast-acting blood-stage antimalarial candidate . The molecule was identified using a phenotypic high-throughput screening approach which has been successfully used to identify new antimalarial chemotypes . Phenotypic screens can be preferable to target-based [...]

LXE408 is an oral antileishmanarial compound that selectively targets the kinetoplastid proteosome vs. the mammalian proteosome. The prior candidate, GNF6702, had solubility-limited oral absorption, which could have been addressed with a specialized formulation but would have increased the cost and limited use in developing countries. A [...]

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 [...]

ETX0282 is an oral prodrug of a class A, C, and D serine β-lactamase inhibitor in clinical development for drug-resistant enterobacterial infections in combination with the beta-lactam drug cefpodoxime proxetil. Impressively ETX0282 had no observed adverse effect levels (NOAELs) of 500 mg/kg/day and 400 mg/kg/day in rat and dog, respectively, [...]