A new era for chagas disease drug discovery?

Progress in Medicinal Chemistry
Martine Keenan, Jason H Chaplin

Abstract

Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed.

Citations

Jul 29, 2015·European Journal of Medicinal Chemistry·Juan Carlos CoaSara M Robledo
Dec 6, 2017·Antimicrobial Agents and Chemotherapy·A S G NefertitiM N C Soeiro
Aug 17, 2018·Expert Review of Clinical Pharmacology·Jadel Müller KratzSergio Sosa-Estani
May 9, 2019·ChemMedChem·Angeliki-Sofia FoscolosJohn M Kelly
Jul 29, 2017·Oxidative Medicine and Cellular Longevity·João Luiz BaldimDaniela Aparecida Chagas-Paula
Jul 28, 2020·PLoS Neglected Tropical Diseases·Anna F FesserMarcel Kaiser
Nov 11, 2020·Antimicrobial Agents and Chemotherapy·Suzana Marques de JesusClaudia Martins Carneiro
Dec 22, 2017·Emerging Topics in Life Sciences·Simon L CroftMichael P Barrett
Oct 10, 2020·ACS Infectious Diseases·Javier Martín-EscolanoRubén Martín-Escolano

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