Evidence map›Paper›PMID 40317875›Full record

ArticleAngewandte Chemie (International ed. in English)2025

The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of Plasmodium Phosphatidylinositol 4-Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria.

John G Woodland, Dina Coertzen, Kathryn J Wicht, Virginia Franco Hidalgo, Charisse Flerida A Pasaje, Luiz C Godoy, Tarrick Qahash, Mmakwena M Mmonwa, Godwin A Dziwornu, Lynn Wambua and 24 more

Abstract read
PubMed Full text at PMC Publisher
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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Novel Inhibitors ofJournal of medicinal chemistry · 2025
    Article
  7. Article
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

34 authors.

John G Woodland *Holistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Dina Coertzen *Department of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Kathryn J WichtHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Virginia Franco HidalgoGlaxoSmithKline, Tres Cantos Medicines Development Campus, Madrid, Spain.
Charisse Flerida A PasajeDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Luiz C GodoyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Tarrick QahashDepartment of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, State College, PA, 16802, USA.
Mmakwena M MmonwaHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Godwin A DziwornuHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Lynn WambuaSouth African Medical Research Council Drug Discovery and Development Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, 7925, South Africa.
Sarah HarriesDepartment of Chemistry, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Constance M KorkorDepartment of Chemistry, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Mathew NjorogeHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Liezl KrugmannHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Dale TaylorHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Meta LeshabaneDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Henrico LangeveldDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Tayla RabieDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Janette ReaderDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Mariëtte van der WattDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Nelius VenterWits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Erica ErlankWits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Ayesha S AswatWits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Lizette L KoekemoerWits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Tomas YeoDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Jin H JeonDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
David A FidockDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Francisco Javier GamoGlaxoSmithKline, Tres Cantos Medicines Development Campus, Madrid, Spain.
Sergio WittlinSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Jacquin C NilesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Manuel LlinasDepartment of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, State College, PA, 16802, USA.
Lauren B CoulsonHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
Lyn-Marié BirkholtzDepartment of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, 0028, South Africa.
Kelly ChibaleHolistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.

Funding

Defining the complex genetic basis of Plasmodium falciparum resistance to artemisinin and quinine and identifying resistance-refractory therapeuticsR01AI185559 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David A Fidock · 2024 to 2026
$1.9M
Repurposing kinase inhibitor chemotypes as antimalarialsR01AI152092 · NIAID · UNIVERSITY OF CAPE TOWN · PI CHIBALE, KELLY, FERRINS, LORI · 2020 to 2024
$1.6M
New tools for antimalarial target identificationR01AI143521 · NIAID · UNIVERSITY OF CAPE TOWN · PI WICHT, KATHRYN JEAN · 2019 to 2023
$709k
Department of Science and Innovation (SAMRC-GIPD) Drug Discovery for Malaria EliminationFuture Leaders-African Independent Research (FLAIR)Gates Foundation INV-033538Medicines for Malaria Venture RD-17-0047Medicines for Malaria Venture RD-19-0001NIAID NIH HHS R01 AI143521NIAID NIH HHS R01 AI152092NIAID NIH HHS R01 AI185559South African Medical Research CouncilThe Department of Science and Innovation and the National Research Foundation South African Research Chair UID 84627the UK Government's Global Challenges Research to L.B.C. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health to K.J.W. R01AI143521the UK Government's Global Challenges Research to L.B.C. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health to K.J.W. R01AI152092the UK Government's Global Challenges Research to L.B.C. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health to K.J.W. R01AI185559
6 · The paper itself

Abstract

New compounds targeting human malaria parasites are critical for effective malaria control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a human ataxia-telangiectasia mutated (ATM) kinase inhibitor that completed Phase I clinical trials as an anticancer agent. We validated its in vitro activity against the two main forms of the Plasmodium falciparum parasite in the human host, viz. the asexual blood (symptomatic) stage and sexual gametocyte (transmission) stage. Resistance selection, cross-resistance, biochemical, and conditional knockdown studies revealed that AZD0156 inhibits P. falciparum phosphatidylinositol 4-kinase type III beta (PfPI4Kβ), a clinically-validated target for the treatment of malaria. Metabolic perturbations, fixed-ratio isobolograms, killing kinetics and morphological evaluation correlated AZD0156 inhibition with other known PI4Kβ inhibitors. The compound showed favorable in vivo pharmacokinetic properties and 81% antimalarial efficacy (4 × 50 mg kg

Indexed as

1-Phosphatidylinositol 4-KinaseAntimalarialsAtaxia Telangiectasia Mutated ProteinsMalariaPlasmodium falciparumProtein Kinase InhibitorsAnimalsHumansMiceMolecular StructureStructure-Activity Relationship1-Phosphatidylinositol 4-KinaseAntimalarialsAtaxia Telangiectasia Mutated ProteinsProtein Kinase InhibitorsAntiplasmodialBiological activityMalariaMedicinal chemistryPhosphatidylinositol 4‐kinase type III beta (PI4Kβ)Repositioning

Identifiers

PMID40317875
PMCPMC12232896

What Socratic holds

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Registered trials

None linked

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.