ASP5286 is an analog of the natural product cyclosporin A that maintains the anti-HCV activity of cyclosporin A by binding to cyclophilin, but was optimized to be less immunosuppresive than cyclosporin A. The macrocycle was identified through semisynthetic derivitization of a related natural product, FR901459. The Astellas team was able to [...]

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 [...]

Pfizer’s PF-07321332 (API of Paxlovid) is an oral, reversible covalent SARS-CoV-2 main protease inhibitor, which received emergency use authorization from the FDA for Covid treatment at the end of 2021. Clinical data showed Paxlovid reducing Covid hospitalization and death by 89%. It was nominated for November’s cover by Mike Koehler [...]

The Entasis broad-spectrum antibiotic, ETX0462 , is both an inhibitor of penicillin-binding proteins (PBPs, the target of beta-lactams) and a beta-lactamase inhibitor (BLI). Reviewer Mike Koehler thought this was a substantial disclosure. “A number of BLIs co-formulated with carbapenems and monobactams are currently on the market. There are a [...]

JNJ-53718678 is a potent and orally available fusion inhibitor of the RSV virus, optimized from a prior oral inhibitor, BMS-433771. The prior inhibitor was challenged by moderate potency, suboptimal PK in preclinical species, limited lung distribution, and potential complications from CYP TDI due to an aminocyclopropyl moiety. The improved [...]