Novel compound series to treat African trypanosomiasis

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African trypanosomiasis
African trypanosomiasis

University: University of Edinburgh

Sector(s): Healthcare & Pharmaceuticals, Life Sciences

About Opportunity:

African Trypanosomiasis is a neglected tropical disease caused by 2 subspecies Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It develops in 2 distinct stages with the 1st, body stage, resulting in cold-like symptoms and the 2nd, central nervous system stage, characterised by severe neurological symptoms. It is fatal if left untreated. It is most prevalent in economically disadvantaged rural communities in Africa which have little health infrastructure. Existing treatments are only available intravenously or are subspecies specific. Moreover, they often have severe side effects, long treatment duration, drug resistance and are expensive. There is therefore an urgent need for new effective and easily administered drugs.


Phosphofructokinase (PFK) is an enzyme in the glycolytic pathway which converts fructose 6-monophosphate to fructose 1, 6-biphosphate on the cascade of converting glucose to pyruvate and ATP. Glycolysis is the sole source of ATP for the bloodstream form of the parasite and blocking it has been shown to kill the parasite much faster than any other drug mechanism. These compounds target the allosteric binding site on the parasite PFK which locks the enzyme in an inactive state. This allosteric pocket is unique to parasite PFK, therefore human phosphofructokinase is completely unaffected by the compounds minimising side effects. The drugs have been extensively characterised both in vitro and in vivo in terms of selectivity, potency and pharmacokinetics and show very favourable properties. Moreover, Trypanosoma brucei’s phosphofructokinase enzyme – compounds interaction have been very well studied by numerous crystal structures which would allow them to be easily modified to further improve properties.

Key Benefits:

  • Novel validated target, well characterised mechanism of action and excellent structure-activity relationship
  • Compounds effective against both subspecies of the parasite and both stages of the disease
  • Orally bioavailable and able to cross the blood brain barrier in favourable proportions
  • Safe and effective in a mouse model with very short treatment duration (1-2 days)
  • Very fast time to completely kill the parasite (minutes vs days for other drug classes)
  • Can be used in combination with current medicines as they have a different mechanism of action


  • New treatments for African Trypanosomiasis

IP Status:

UK patent application protecting the lead series.

Priority date 01/12/2017


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