QPX7728 is an ultrabroad-spectrum beta-lactamase inhibitor with activity against both serine and zinc metallo-beta-lactamases, in contrast to approved beta-lactamase inhibitors such as relebactam which are only active against serine metalloproteases. Interestingly, the boron of the molecule coordinates to serine hydroxyl groups in serine [...]

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.

This month’s cover molecule, Pfizer’s PF-07321332 (nirmatrelvir, API of Paxlovid) is an oral, reversible covalent SARS-CoV-2 main protease inhibitor, which has been submitted to the FDA by Pfizer for emergency approval for Covid treatment. Interim data showed Paxlovid reducing Covid hospitalization and death by 89%. It was nominated for this month’s [...]

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.

Infection with the malaria parasite, Plasmodium falciparum, is a leading cause of fatality in the tropical regions of the world, with over 240M infections and >600k deaths each year. Currently, over half of the world population is at risk of infection and with the rise of resistance against current treatments, the need for new antimalarials is clear. At the ACS Fall 2024 conference in Denver, CO, Novartis outlined the structure and discovery story of NVP-IWY357, a novel antimalarial that has no cross-resistance to current drugs and the potential to achieve a single-dose cure.