Publication
Title
DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc₁
Author
Abstract
New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc 1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc 1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.
Language
English
Source (journal)
Science translational medicine. - -
Publication
2023
ISSN
1946-6234
DOI
10.1126/SCITRANSLMED.ADH9902
Volume/pages
15 :726 (2023)
Article Reference
eadh9902
ISI
001147945500005
Pubmed ID
38091406
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 27.02.2024
Last edited 05.03.2024
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