Evidence mapPaperPMID 40412380Full record

ArticleCell chemical biology2025

The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels.

Irene Molina, Ryan Mansell, Rui Liang, Benigno Crespo, Margarita Puente, Virginia Franco, Sara Viera, Isabel Camino, Anas Saadeddin, Peter Bellotti and 14 more

Abstract read
In one paragraph

Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

24 authors.

Irene MolinaGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Ryan MansellDepartment of Microbiology & Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Rui LiangSanders Tri-Institutional Therapeutics Discovery Institute, New York, NY 10065, USA.
Benigno CrespoGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Margarita PuenteDiscovery Chemistry, GSK, Tres Cantos, CP28760 Madrid, Spain.
Virginia FrancoGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Sara VieraGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Isabel CaminoR&D Pre-clinical Sciences DMPK, Tres Cantos, CP28760 Madrid, Spain.
Anas SaadeddinR&D Pre-clinical Sciences DMPK, Tres Cantos, CP28760 Madrid, Spain.
Peter BellottiDepartment of Pharmacology, Weill Cornell Medicine, New York, NY 10021, USA.
Annie LeungDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10021, USA.
Sam HenningDepartment of Microbiology & Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Shan SunSanders Tri-Institutional Therapeutics Discovery Institute, New York, NY 10065, USA.
Mikayla HerringDepartment of Microbiology & Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Celia LopezGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Carmen CuevasGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Peter PogányData and Predictive Sciences, Research Technologies, R&D, GSK Medicine Research Centre, Stevenage SG12NY, UK.
Beatriz UronesGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Leigh BaxtSanders Tri-Institutional Therapeutics Discovery Institute, New York, NY 10065, USA.
Esther FernándezGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain.
Jacob GeriDepartment of Pharmacology, Weill Cornell Medicine, New York, NY 10021, USA.
Laura KirkmanDepartment of Microbiology & Immunology, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10021, USA.
Björn F C KafsackDepartment of Microbiology & Immunology, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: kafsacklab@gmail.com.
Lydia Mata-CanteroGlobal Health Medicines R&D, GSK, Tres Cantos, CP28760 Madrid, Spain. Electronic address: lydia.c.mata@gsk.com.

Funding

Regulation of Sexual Differentiation in Malaria ParasitesR01AI141965 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI KAFSACK, BJORN FELIX CAESAR · 2019 to 2023
$2.8M
NIAID NIH HHS R01 AI141965
6 · The paper itself

Abstract

Spreading resistance to front-line treatments necessitate the search for new classes of antimalarials. Limitations of standard screening conditions lead us to develop an assay using culture media that more closely reflects nutrient levels in human serum to reveal new therapeutically relevant parasite pathways. Our approach was validated by testing 22k compounds followed by a full 750k compound screen and identified 29 chemotypes with higher activity in nutrient restricted media that were further characterized. Through a combination of chemo-genomics and innovative photocatalytic proximity labeling proteomics, we identified the target of two compounds as the CLAG3 component of the plasmodial surface anion channel (PSAC). Strikingly, every one of the other 29 chemotypes selected was also found to block PSAC activity, highlighting the importance of this nutrient channel for parasite survival under physiological conditions. The effect of PSAC inhibitors in the in vivo humanized mouse model was confirmed.

Indexed as

AntimalarialsMalariaNutrientsPlasmodium falciparumProtozoan ProteinsAnimalsHumansMicePhenotypeAntimalarialsNutrientsProtozoan ProteinsantimalarialCLAG3HTSinhibitorsmalarianutrient-restricted-mediaP. falciparumphysiological-mediaPSACscreening

Identifiers

PMID40412380
PMCPMC12181053

What Socratic holds

Textmetadata
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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.