Dissemin is shutting down on January 1st, 2025

Published in

Wiley, ChemMedChem, 7(8), p. 1127-1137, 2013

DOI: 10.1002/cmdc.201300072

Links

Tools

Export citation

Search in Google Scholar

From On-Target to Off-Target Activity: Identification and Optimisation of Trypanosoma brucei GSK3 Inhibitors and Their Characterisation as Anti-Trypanosoma brucei Drug Discovery Lead Molecules

Journal article published in 2013 by Andrew Woodland, Raffaella Grimaldi, Torsten Luksch, Laura A. T. Cleghorn ORCID, Kayode K. Ojo, Wesley C. Van Voorhis, Ruth Brenk, Julie A. Frearson, Ian H. Gilbert, Paul G. Wyatt
This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

Abstract

Human African trypanosomiasis (HAT) is a life-threatening disease with approximately 30 000–40 000 new cases each year. Trypanosoma brucei protein kinase GSK3 short (TbGSK3) is required for parasite growth and survival. Herein we report a screen of a focused kinase library against T. brucei GSK3. From this we identified a series of several highly ligand-efficient TbGSK3 inhibitors. Following the hit validation process, we optimised a series of diaminothiazoles, identifying low-nanomolar inhibitors of TbGSK3 that are potent in vitro inhibitors of T. brucei proliferation. We show that the TbGSK3 pharmacophore overlaps with that of one or more additional molecular targets.