Evidence map›Paper›PMID 40035755›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).

Sesh A Sundararaman, Justin J Miller, Ellora C Daley, Kelsey A O'Brien, Paulina Kasak, Abigail M Daniels, Rachel L Edwards, Kenneth M Heidel, Darean A Bague, Madeleine A Wilson and 13 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Sesh A SundararamanDepartment of Pediatrics, Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID 0000-0001-9875-8378
Justin J MillerDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0001-9400-8916
Ellora C DaleyDepartment of Pediatrics, Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Kelsey A O'BrienDepartment of Pediatrics, Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Paulina KasakCollege of Health Professions, Thomas Jefferson University, Philadelphia, PA 19107.ORCID 0009-0007-3791-8818
Abigail M DanielsDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-6542-1960
Rachel L EdwardsDepartment of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110.
Kenneth M HeidelDepartment of Chemistry, George Washington University, Washington, DC 20052.
Darean A BagueDepartment of Chemistry, George Washington University, Washington, DC 20052.
Madeleine A WilsonDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Andrew J KoelperDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Elexi C KourtoglouDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Alex D WhiteDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Sloan A AugustDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Georgia A AppleDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.ORCID 0009-0004-3678-7930
Regis W RouambaDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Anthony J DurandDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
John J EstebDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.ORCID 0009-0005-9744-5608
Florian L MullerLindonlight Collective, Houston, TX 77021.
R Jeremy JohnsonDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Geoffrey C HoopsDepartment of Chemistry and Biochemistry, Butler University, Indianapolis, IN 46208.
Cynthia S DowdDepartment of Chemistry, George Washington University, Washington, DC 20052.
Audrey R Odom JohnDepartment of Pediatrics, Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID 0000-0001-8395-8537

Funding

MEP pathway resistance in Plasmodium falciparumR01AI103280 · NIAID · WASHINGTON UNIVERSITY · PI Audrey Ragan Odom John · 2013 to 2026
$5.5M
Structure-based microbially targeted prodrugsR01AI171514 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI DOWD, CYNTHIA SCHIECK, JEZ, JOSEPH MARTIN · 2022 to 2025
$4.0M
Inhibition of MEP pathway Isoprenoid BiosynthesisR01AI123433 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI DOWD, CYNTHIA SCHIECK, MEYERS, MARVIN J · 2016 to 2020
$2.6M
Combined Adult and Pediatric Infectious Disease Postdoctoral Training GrantT32AI118684 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Rahul Manu Kohli, Audrey Ragan Odom John · 2016 to 2026
$2.3M
Training in Microbial Pathogenesis and GenomicsT32AI141393 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GOULIAN, MARK D, ZHU, JUN · 2019 to 2023
$1.3M
Children's Hospital of Philadelphia (CHOP) K-Readiness Pilot GrantDoris Duke Charitable Foundation (DDCF) Paragon of Research Excellence AwardHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI103280HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI123433HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI171514HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI118684HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32AI141393Indiana Academy of Science (IAS) Senior Research GrantNIAID NIH HHS R01 AI103280NIAID NIH HHS R01 AI123433NIAID NIH HHS R01 AI171514NIAID NIH HHS T32 AI118684NIAID NIH HHS T32 AI141393Pediatric Infectious Diseases Society (PIDS) PIDS-St. Jude Children's Research Hospital Fellowship Award in Basic and Translational Science
6 · The paper itself

Abstract

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards

Indexed as

AntimalarialsErythrocytesEsterasesMalaria, FalciparumPeptide HydrolasesPlasmodium falciparumProdrugsHumansProtozoan ProteinsStructure-Activity Relationshipacylaminoacyl-peptidaseAntimalarialsEsterasesPeptide HydrolasesProdrugsProtozoan Proteinsdrug discoveryenzymehost parasite interactionsmalariaprodrug

Identifiers

PMID40035755
PMCPMC11912422

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.