RLA-4735

RLA-4735 is a synthetic 1,2,4-trioxolane (ozonide) endoperoxide antimalarial agent designed to address artemisinin partial resistance (ART-R) and formulation/solubility challenges associated with its predecessor, artefenomel. Developed by researchers at the University of California San Francisco (UCSF) and licensed to Tatara Therapeutics, RLA-4735 is a racemic mixture of trans-3'-substituted trioxolane diastereomers, with its single-enantiomer form designated as RLA-5764. Mechanistically, RLA-4735 is activated by ferrous iron (heme) within the parasite's digestive vacuole, generating highly reactive radical species that damage critical parasite proteins and lipids, leading to rapid parasite clearance. It exhibits potent ex vivo activity against Plasmodium falciparum isolates, including those with reduced susceptibility to dihydroartemisinin, and demonstrates single-exposure efficacy in murine malaria models.

Other names

(±)-151(±)-2racemic RLA-4735