ArticleChemMedChem2013
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.
Article in ChemMedChem, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Late-Stage Functionalization via Thianthrenation: A Reaction Enabling Rapid Preparation of Drug Beads for Chemical Pulldown.Journal of medicinal chemistry · 2026Article
- Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.Journal of medicinal chemistry · 2023Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Further Investigations of Nitroheterocyclic Compounds as Potential Antikinetoplastid Drug Candidates.Biomolecules · 2023Review
- Repositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis.Journal of medicinal chemistry · 2022Article
- Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-Journal of medicinal chemistry · 2020Article
- A Radioactive-free Kinase Inhibitor Discovery Assay Against theBio-protocol · 2020Article
- Indirubin Analogues InhibitAntimicrobial agents and chemotherapy · 2019Article
- Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.Journal of medicinal chemistry · 2019Article
- Identification of inhibitors of an unconventional Trypanosoma brucei kinetochore kinase.PloS one · 2019Article
- Article
- Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need.Nature reviews. Microbiology · 2017Review
- Synthesis and biological evaluation of N-cyanoalkyl-, N-aminoalkyl-, and N-guanidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents.Bioorganic & medicinal chemistry · 2016Article
- Glycogen Synthase Kinase 3β Promotes the Endocytosis of Transferrin in the African Trypanosome.ACS infectious diseases · 2016Article
- Enzyme Activity Assays for Protein Kinases: Strategies to Identify Active Substrates.Current drug discovery technologies · 2016Review
- Kinases as druggable targets in trypanosomatid protozoan parasites.Chemical reviews · 2014Review
- The design and synthesis of potent and selective inhibitors of Trypanosoma brucei glycogen synthase kinase 3 for the treatment of human african trypanosomiasis.Journal of medicinal chemistry · 2014Article
- Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug discovery.MedChemComm · 2014Article
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Authors and funding
10 authors.
Funding
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.
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