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Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors. 2012
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, U.K.
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 (IC(50) = 2 nM) and T. brucei (EC(50) = 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.
Related Publications
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
March 1998,
Journal of medicinal chemistry,
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
December 2017,
Journal of medicinal chemistry,
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
December 2010,
Bioorganic & medicinal chemistry letters,
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Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
November 2011,
Antimicrobial agents and chemotherapy,
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Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
March 2008,
Bioorganic & medicinal chemistry,
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Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
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European journal of medicinal chemistry,
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Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
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ChemMedChem,
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
October 1992,
Journal of medicinal chemistry,
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
March 2022,
ACS medicinal chemistry letters,
Stephen Brand, and
Laura A T Cleghorn, and
Stuart P McElroy, and
David A Robinson, and
Victoria C Smith, and
Irene Hallyburton, and
Justin R Harrison, and
Neil R Norcross, and
Daniel Spinks, and
Tracy Bayliss, and
Suzanne Norval, and
Laste Stojanovski, and
Leah S Torrie, and
Julie A Frearson, and
Ruth Brenk, and
Alan H Fairlamb, and
Michael A J Ferguson, and
Kevin D Read, and
Paul G Wyatt, and
Ian H Gilbert
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MedChemComm,
