Sharing of Artefenomel-like Trioxolane Analogs for Microsome Stability Testing

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Artemisinin combination therapy (ACT) is the standard of care in treating uncomplicated malaria, while newer synthetic endoperoxides like artefenomel are being actively studied in clinical trials. Adam Renslo, in the Department of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF), is exploring artefenomel-like trioxolane analogs bearing a novel substitution pattern that may deliver improved physiochemical properties. To assist the Renslo Lab in driving this program toward clinical candidate selection, Medicines for Malaria Venture (MMV) is supporting the Renslo Lab in assessing the solubility, lipophilicity, and metabolic stability of frontrunner compounds using appropriate in vitro ADME assays. The resulting data will be a key factor in the selection of the best analogs for further in vivo evaluation. Given the extent of work and progress in the endoperoxide area, new compounds will only be of interest if their pharmacokinetics and potency support very low single dose potential with no alteration of parasite clearance between sensitive and resistant parasites. These early studies will help to assess the Renslo Lab compounds against this high bar.