ArticleJournal of medicinal chemistry2013
Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 75 citations in OpenAlex.
- Design, Synthesis, Antiproliferative Potency and In Silico Studies of Novel Alkynyl Quinazolines as Potential EGFR Inhibitors.International journal of molecular sciences · 2026Article
- Optimization of Quinazolines for Inhibition ofACS medicinal chemistry letters · 2025Article
- Aminopyridines in the development of drug candidates against protozoan neglected tropical diseases.Future medicinal chemistry · 2024Review
- Utilization of Supervised Machine Learning to Understand Kinase Inhibitor Toxophore Profiles.International journal of molecular sciences · 2023Article
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead forJournal of medicinal chemistry · 2020Article
- Structure-Bioactivity Relationships of Lapatinib Derived Analogs againstACS medicinal chemistry letters · 2020Article
- Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.PLoS neglected tropical diseases · 2019Article
- Kinetoplast Division Factors in a Trypanosome.Trends in parasitology · 2019Review
- Improvement of Aqueous Solubility of Lapatinib-Derived Analogues: Identification of a Quinolinimine Lead for Human African Trypanosomiasis Drug Development.Journal of medicinal chemistry · 2019Article
- High Throughput and Computational Repurposing for Neglected Diseases.Pharmaceutical research · 2018Review
- Series of Alkynyl-Substituted Thienopyrimidines as Inhibitors of Protozoan Parasite Proliferation.ACS medicinal chemistry letters · 2018Article
- Optimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation.ACS infectious diseases · 2018Article
- Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation.European journal of medicinal chemistry · 2017Article
- Novel lead compounds in pre-clinical development against African sleeping sickness.MedChemComm · 2017Review
- AEE788 Inhibits Basal Body Assembly and Blocks DNA Replication in the African Trypanosome.Molecular pharmacology · 2017Article
- Antiparasitic Lead Discovery: Toward Optimization of a Chemotype with Activity Against Multiple Protozoan Parasites.ACS medicinal chemistry letters · 2017Article
- Novel Effects of Lapatinib Revealed in the African Trypanosome by Using Hypothesis-Generating Proteomics and Chemical Biology Strategies.Antimicrobial agents and chemotherapy · 2017Article
- Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HTJournal of medicinal chemistry · 2016Article
- Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei . Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.