DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc 1

• DOI: 10.1126/scitranslmed.adh9902
• Publication Date: 2023-12-13T18:58:21Z
• Authors: Stéphanie Braillard; Martine Keenan; Karen J. Breese; Jacob Heppell; Michael Abbott; Rafiqul Islam; David M. Shackleford; Kasiram Katneni; Elly Crighton; Gong Chen; Rahul Patil; Given Lee; Karen L. White; Sandra Carvalho; Richard J. Wall; Giulia Chemi; Fabio Zuccotto; Silvia González; Maria Marco; Julianna Deakyne; David Standing; Gino Brunori; Jonathan J. Lyon; Pablo Castañeda-C...; Isabel Camino; Maria S. Martinez...; Bilal Zulfiqar; Vicky M. Avery; Pim-Bart Feijens; Natascha Van Pelt; An Matheeussen; Sarah Hendrickx; Louis Maes; Guy Caljon; Vanessa Yardley; Susan Wyllie; Susan A. Charman; Eric Chatelain
• Keywords: Visceral; 570; 0303 health sciences; Leishmaniasi; Animal; Medical biotechnology; 610; 600; Rats; Animals; Disease Models, Animal; Leishmaniasis; Leishmaniasis, Visceral; Rats; Disease Models, Animal; 03 medical and health sciences; Disease Models; Animals; Leishmaniasis, Visceral; Biomedical engineering; Leishmaniasis

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field urgently required. Despite concerted efforts over last several years, number of new chemical entities suitable clinical development treatment Leishmania remains low. Here, we describe discovery preclinical DNDI-6174, an inhibitor cytochrome bc 1 complex activity originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required progression into development. In addition good metabolic stability pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro against variety species can reduce parasite burden animal models infection, with potential approach sterile cure. No major flags were preliminary safety studies, including exploratory 14-day toxicology study rat. is acceptable properties enter leishmaniasis.