1111178-07-4Relevant academic research and scientific papers
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
Woodland, Andrew,Grimaldi, Raffaella,Luksch, Torsten,Cleghorn, Laura A. T.,Ojo, Kayode K.,VanVoorhis, Wesley C.,Brenk, Ruth,Frearson, Julie A.,Gilbert, Ian H.,Wyatt, Paul G.
, p. 1127 - 1137 (2013/07/26)
Human African trypanosomiasis (HAT) is a life-threatening disease with approximately 30000-40000 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 invitro inhibitors of T.brucei proliferation. We show that the TbGSK3 pharmacophore overlaps with that of one or more additional molecular targets.
