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Home > Scientific articles
Oct 2021
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DNDI-6148: A novel benzoxaborole preclinical candidate for the treatment of visceral leishmaniasis

Journal of Medicinal Chemistry

by Mowbray CE, Braillard S, Glossop PA, Whitlock GA, Jacobs RT, Speake J, Pandi B, Nare B, Maes L, Yardley V, Freund Y, Wall RJ, Carvalho S, Bello D, Van den Kerkhof M, Caljon G, Gilbert IH, Corpas-Lopez V, Lukac I, Patterson S, Zuccotto F, Wyllie S. Journal of Medicinal Chemistry 2021, 64 (21): 16159-16176. doi: 10.1021/acs.jmedchem.1c01437

Summary: There is an urgent need for safe, short-course, low-cost oral treatments to combat visceral leishmaniasis. The authors describe the development and optimization of a benzoxaborole series, which led to the identification of compounds with potent in vitro and in vivo antileishmanial activity. The lead compound (DNDI-6148) combines impressive in vivo efficacy (>98% reduction in parasite burden) with pharmaceutical properties suitable for onward development and an acceptable safety profile. Detailed mode of action studies confirm that DNDI-6148 acts principally through the inhibition of Leishmania cleavage and polyadenylation specificity factor (CPSF3) endonuclease. As a result of these studies and its promising profile, DNDI-6148 has been declared a preclinical candidate for the treatment of visceral leishmaniasis.

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Translational research Visceral leishmaniasis

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