Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase

Brimacombe, Kyle R.; Walsh, Martin J.; Liu, Li; Vásquez-Valdivieso, Montserrat
G.; Morgan, Hugh P.; McNae, Iain; Fothergill-Gilmore, Linda A.; A. M. Michels, Paul; Auld, Douglas S.; Simeonov, Anton; Walkinshaw, Malcolm D.; Shen, Min; Boxer, Matthew B.

doi:10.1021/ml400259d.s001

ml400259d_si_001.pdf (568.64 kB)

Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase

journal contribution

posted on 2014-01-09, 00:00 authored by Kyle R. Brimacombe, Martin J. Walsh, Li Liu, Montserrat G. Vásquez-Valdivieso, Hugh P. Morgan, Iain McNae, Linda A. Fothergill-Gilmore, Paul A. M. Michels, Douglas S. Auld, Anton Simeonov, Malcolm D. Walkinshaw, Min Shen, Matthew B. Boxer

Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist Trypanosoma brucei. The glycolytic pathway has been identified as the sole mechanism for ATP generation in the infective stage of these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in particular, have shown promise as potential drug targets. Herein, we describe the discovery of ML251, a novel nanomolar inhibitor of T. brucei PFK, and the structure–activity relationships within the series.