ArticleNature2018
Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis.
Erratum issuedAbstract readValidation Study
In one paragraph
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers.
0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
–field-weighted citation impact
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed.
- Safety, tolerability and pharmacokinetics of DNDI-6148, a novel agent for leishmaniasis: A randomized, controlled, single ascending dose study in healthy participants.British journal of clinical pharmacology · 2026Trial
- Towards precision antileishmanial drug discovery: Integrating multi-omics, functional genomics, artificial intelligence and host-directed therapeutics.Molecular biology reports · 2026Review
- Identification of New Anti-Trypanosoma brucei Leads: An Integrated CRK12-Guided Virtual Screen With Experimental Validation.Chemical biology & drug design · 2026Article
- Late-Stage Functionalization via Thianthrenation: A Reaction Enabling Rapid Preparation of Drug Beads for Chemical Pulldown.Journal of medicinal chemistry · 2026Article
- Using Unbiased Chemical Proteomics Approaches to Explore the Target Landscape of the Resistance Refractory 7-Azaindole MMV022224 inACS infectious diseases · 2026Article
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Enhancing kinase-inhibitor activity and selectivity prediction through contrastive learning.Nature communications · 2025Article
- Discovery and Characterization of Cell-Permeable Inhibitors ofACS infectious diseases · 2025Article
- Discovery of Novel CRK12 Inhibitors for the Treatment of Human African Trypanosomiasis: An Integrated Computational and Experimental Approach.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Progress in antileishmanial drugs: Mechanisms, challenges, and prospects.PLoS neglected tropical diseases · 2025Review
- Activity-based chemoproteomic profiling reveals the active kinome ofFrontiers in pharmacology · 2025Article
- Editorial: Drug discovery for leishmaniasis and chagas disease: compound design and therapeutic strategies.Frontiers in pharmacology · 2025Article
- Identification of novel compounds againstComputational and structural biotechnology journal · 2025Article
- Uncovering the Mechanism of Action of Antiprotozoal Agents: A Survey on Photoaffinity Labeling Strategy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of Novel Antileishmanial Chemotypes By High-Throughput Virtual and In Vitro Screening.Acta parasitologica · 2024Article
- In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells.Scientific reports · 2024Article
- Effect of Hydroxyurea on Morphology, Proliferation, and Protein Expression onInternational journal of molecular sciences · 2024Article
- Identification of Novel Flavonoids and Ansa-Macrolides with Activities againstPathogens (Basel, Switzerland) · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
32 authors.
Susan WyllieDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Michael ThomasDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Stephen PattersonDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Sabrinia CrouchGlobal Health R&D, GlaxoSmithKline, Tres Cantos, Spain.
Manu De RyckerDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Rhiannon LoweDavid Jack Centre for R&D, GlaxoSmithKline, Ware, UK.
Stephanie GreshamDavid Jack Centre for R&D, GlaxoSmithKline, Ware, UK.
Michael D UrbaniakDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Thomas D OttoWellcome Sanger Institute, Cambridge, UK.
Laste StojanovskiDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Frederick R C SimeonsDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Sujatha ManthriDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Lorna M MacLeanDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Fabio ZuccottoDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Nadine HomeyerDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Hannah PflaumerCellzome GmbH, A GlaxoSmithKline Company, Heidelberg, Germany.
Markus BoescheCellzome GmbH, A GlaxoSmithKline Company, Heidelberg, Germany.
Lalitha SastryDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Paul ConnollyGlaxoSmithKline, New Frontiers Science Park, Harlow, UK.
Sebastian AlbrechtDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Matt BerrimanWellcome Sanger Institute, Cambridge, UK.
Gerard DrewesCellzome GmbH, A GlaxoSmithKline Company, Heidelberg, Germany.
David W GrayDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Sonja Ghidelli-DisseCellzome GmbH, A GlaxoSmithKline Company, Heidelberg, Germany.
Susan DixonGlobal Health R&D, GlaxoSmithKline, Stockley Park West, Uxbridge, UK.
Jose M FiandorGlobal Health R&D, GlaxoSmithKline, Tres Cantos, Spain.
Paul G WyattDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Michael A J FergusonDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Alan H FairlambDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK.
Timothy J MilesGlobal Health R&D, GlaxoSmithKline, Tres Cantos, Spain. tim.j.miles@gsk.com.
Kevin D ReadDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK. k.read@dundee.ac.uk.
Ian H GilbertDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK. i.h.gilbert@dundee.ac.uk.
Funding
Wellcome Trust 079838Wellcome Trust 092340Wellcome Trust 098051Wellcome Trust 100476Wellcome Trust 101842Wellcome Trust 105021Wellcome Trust 203134Wellcome Trust 203134/Z/16/ZWellcome Trust 204672/Z/16/Z
Abstract
Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis.
Indexed as
Molecular Targeted TherapyAnimalsCyclin-Dependent Kinase 9Cyclin-Dependent KinasesDisease Models, AnimalHumansLeishmania donovaniLeishmaniasis, VisceralMiceMolecular Docking SimulationProteomeProteomicsPyrazolesPyrimidinesReproducibility of ResultsSubstrate SpecificityCDK9 protein, humanCyclin-Dependent Kinase 9Cyclin-Dependent KinasesProteomePyrazolesPyrimidines
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