Identification of ML251, a potent inhibitor of T. brucei and T. cruzi phosphofructokinase

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)12-17
Number of pages6
JournalBioorganic & Medicinal Chemistry Letters
Volume5
Issue number1
Early online date30 Oct 2013
DOIs
Publication statusPublished - 9 Jan 2014

Keywords

  • glycolysis
  • high-throughput screening
  • inhibitors
  • phosphofructokinase
  • trypanosoma brucei
  • Trypanosoma cruzi/genetics

Fingerprint

Dive into the research topics of 'Identification of ML251, a potent inhibitor of T. brucei and T. cruzi phosphofructokinase'. Together they form a unique fingerprint.

Cite this