958563-25-2Relevant academic research and scientific papers
Discovery of a novel class of orally active trypanocidal N-Myristoyltransferase inhibitors
Brand, Stephen,Cleghorn, Laura A. T.,McElroy, Stuart P.,Robinson, David A.,Smith, Victoria C.,Hallyburton, Irene,Harrison, Justin R.,Norcross, Neil R.,Spinks, Daniel,Bayliss, Tracy,Norval, Suzanne,Stojanovski, Laste,Torrie, Leah S.,Frearson, Julie A.,Brenk, Ruth,Fairlamb, Alan H.,Ferguson, Michael A. J.,Read, Kevin D.,Wyatt, Paul G.,Gilbert, Ian H.
supporting information; experimental part, p. 140 - 152 (2012/03/09)
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.
