Dissemin is shutting down on January 1st, 2025

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American Chemical Society, Journal of Medicinal Chemistry, 1(55), p. 140-152, 2011

DOI: 10.1021/jm201091t

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Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

Journal article published in 2011 by Stephen Brand, Laura A. T. Cleghorn ORCID, Stuart P. McElroy, David A. Robinson, Victoria C. Smith, Irene Hallyburton, Justin R. Harrison, Neil R. Norcross, Daniel Spinks, Tracy Bayliss, Suzanne Norval, Laste Stojanovski, Leah S. Torrie, Julie A. Frearson, Ruth Brenk and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.