Evidence map›Paper›PMID 41131905›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.

Henrico Langeveld, Keletso Maepa, Marché Maree, Jessica L Thibaud, Nicolaas Salomane, Rosie Bridgwater, Mufuliat T Famodimu, Luiz C Godoy, Charisse Flerida A Pasaje, Nonlawat Boonyalai and 14 more

Abstract read
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In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Henrico LangeveldDepartment of Biochemistry, Genetics and Microbiology, Hatfield, Pretoria, 0028, South Africa.
Keletso MaepaSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Marché MareeDepartment of Biochemistry, Genetics and Microbiology, Hatfield, Pretoria, 0028, South Africa.
Jessica L ThibaudDepartment of Biochemistry, Stellenbosch University, Stellenbosch, 7602, South Africa.
Nicolaas SalomaneSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Rosie BridgwaterLSHTM Malaria Centre, London School of Hygiene and Tropical Medicine, London, UK.
Mufuliat T FamodimuLSHTM Malaria Centre, London School of Hygiene and Tropical Medicine, London, UK.
Luiz C GodoyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Charisse Flerida A PasajeDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Nonlawat BoonyalaiDivision of Biological Chemistry and Drug Discovery, Wellcome Centre for Anti-Infectives Research, University of Dundee, Dundee, UK.
Mariana Laureano de SouzaDepartment of Pediatrics, School of Medicine, University of California, San Diego, CA, 92093, USA.
Justin FongDepartment of Pediatrics, School of Medicine, University of California, San Diego, CA, 92093, USA.
Tayla RabieDepartment of Biochemistry, Genetics and Microbiology, Hatfield, Pretoria, 0028, South Africa.
Mariëtte van der WattInstitute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria, 0028, South Africa.
Rensu P TheartDepartment of Electrical and Electronic Engineering, Stellenbosch University, Stellenbosch, 7602, South Africa.
Sonja Ghidelli-DisseCellzome GmbH, GSK Company, Heidelberg, Germany.
Jacquin C NilesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Marcus C S LeeDivision of Biological Chemistry and Drug Discovery, Wellcome Centre for Anti-Infectives Research, University of Dundee, Dundee, UK.
Elizabeth A WinzelerDepartment of Pediatrics, School of Medicine, University of California, San Diego, CA, 92093, USA.
Michael J DelvesLSHTM Malaria Centre, London School of Hygiene and Tropical Medicine, London, UK.
Kelly ChibaleSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Kathryn J WichtSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Lauren B CoulsonSouth African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Lyn-Marié BirkholtzDepartment of Biochemistry, Genetics and Microbiology, Hatfield, Pretoria, 0028, South Africa.ORCID 0000-0001-5888-2905

Funding

Gates Foundation INV-039628Institute for Sustainable Malaria Control, University of PretoriaMedicines for Malaria Venture RD-19-001Medicines for Malaria Venture RD-21-1003South African Medical Research CouncilSouth African National Research Foundation UID84672UKRI MRC Career Development Award MR/V010034/1
6 · The paper itself

Abstract

Kinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nuclear division, segregation, and cytokinesis. We evaluated the potential of human Aurora kinase (Aur) inhibitors to prevent P. falciparum development by targeting members of the Aurora-related kinase (Ark) family in this parasite. Several human AurB inhibitors exhibited multistage potency (< 250 nM) against all proliferative stages of parasite development, including asexual blood stages, liver schizonts, and male gametes. The most potent compounds, hesperadin, TAE684, and AT83, exhibited > 1000x selectivity towards the parasite. Importantly, we identified PfArk1 as the principal vulnerable Ark family member, with specific inhibition of PfArk1 as the primary target for hesperadin. Hesperadin's whole-cell and protein activity validates it as a unique PfArk1 tool compound. Inhibition of PfArk1 results in the parasite's inability to complete mitotic processes, presenting with unsegregated, multi-lobed nuclei caused by aberrant microtubule organization. This suggests PfArk1 is the main Aur mitotic kinase in proliferative stages of Plasmodium, characterized by bifunctional AurA and B activity. This paves the way for drug-discovery campaigns based on hesperadin targeting PfArk1.

Indexed as

AntimalarialsAurora KinasesPlasmodium falciparumProtein Kinase InhibitorsCell CycleHumansAntimalarialsAurora KinasesProtein Kinase InhibitorsAnti‐cancer inhibitorsAntimalarial drug discoveryAurora kinaseCell cycle regulationPlasmodium

Identifiers

PMID41131905
PMCPMC12707362

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.