pateamine A

Pateamine A (PatA) is a potent, cell-permeable marine macrodiolide natural product originally isolated from the marine sponge *Mycale hentscheli* off the coast of New Zealand. It acts as a first-in-class interfacial inhibitor of eukaryotic translation initiation by binding to and sequestering the DEAD-box RNA helicase eukaryotic initiation factor 4A (eIF4A), specifically the eIF4A1 and eIF4A2 isoforms. This binding clamps eIF4A onto mRNA, preventing its participation in the assembly of the eIF4F complex and stalling ribosome recruitment. Pateamine A also interacts with eIF4A3 to inhibit nonsense-mediated mRNA decay (NMD) and targets the DEAD-box helicase DDX3X. It exhibits potent antiproliferative, proapoptotic, and immunosuppressive activities, and is being investigated for the treatment of various cancers, including pancreatic cancer, triple-negative breast cancer, and chronic lymphocytic leukemia (CLL), as well as cachexia and viral infections (such as coronaviruses). EpiTranslations, a spinout co-founded by researchers from Baylor University and Columbia University, is developing pateamine A derivatives and combination therapies for oncology indications.

Other names

(-)-pateamine APatApateamine-A