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Herein we report a screen of a focused kinase library against <jats:italic>T.\u2005brucei<\/jats:italic> GSK3. From this we identified a series of several highly ligand\u2010efficient <jats:italic>Tb<\/jats:italic>GSK3 inhibitors. Following the hit validation process, we optimised a series of diaminothiazoles, identifying low\u2010nanomolar inhibitors of <jats:italic>Tb<\/jats:italic>GSK3 that are potent in\u2005vitro inhibitors of <jats:italic>T.\u2005brucei<\/jats:italic> proliferation. We show that the <jats:italic>Tb<\/jats:italic>GSK3 pharmacophore overlaps with that of one or more additional molecular targets.<\/jats:p>","DOI":"10.1002\/cmdc.201300072","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T08:38:28Z","timestamp":1371199108000},"page":"1127-1137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["From On\u2010Target to Off\u2010Target Activity: Identification and Optimisation of <i>Trypanosoma brucei<\/i> GSK3 Inhibitors and Their Characterisation as Anti\u2010<i>Trypanosoma brucei<\/i> Drug Discovery Lead Molecules"],"prefix":"10.1002","volume":"8","author":[{"given":"Andrew","family":"Woodland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Grimaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Luksch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A. 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