Evidence map›Paper›PMID 40779626›Full record

ArticleScience advances2025

Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.

Matthew T Klope, Poulami Talukder, Brian R Blank, Sevil Chelebieva, Jun Chen, Shaun D Fontaine, Ryan L Gonciarz, Priyadarshini Jaishankar, Grace J Lee, Jennifer Legac and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 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. Double Mutations inbioRxiv : the preprint server for biology · 2026
    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

23 authors.

Matthew T KlopeDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2801-6448
Poulami TalukderDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Brian R BlankDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Sevil ChelebievaDominican University of California, San Rafael, CA, USA.
Jun ChenDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Shaun D FontaineDepartments of Chemistry and In Vivo Pharmacology, Tatara Therapeutics, San Francisco, CA, USA.ORCID 0000-0002-5800-0391
Ryan L GonciarzDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6600-7032
Priyadarshini JaishankarDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0005-2013-8941
Grace J LeeDepartments of Chemistry and In Vivo Pharmacology, Tatara Therapeutics, San Francisco, CA, USA.
Jennifer LegacInfectious Diseases Research Collaboration, Kampala, Uganda.
Vineet MathurDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Avani NarayanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Martin OkitwiInfectious Diseases Research Collaboration, Kampala, Uganda.ORCID 0000-0003-2712-2174
Stephen OrenaInfectious Diseases Research Collaboration, Kampala, Uganda.
Nicholas S SettineriAdvanced Light Source, Lawrence Berkeley National Laboratory and Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.ORCID 0000-0003-0272-454X
Juan A TapiaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5809-0537
Yoweri TaremwaInfectious Diseases Research Collaboration, Kampala, Uganda.
Patrick K TumwebazeInfectious Diseases Research Collaboration, Kampala, Uganda.
Aswathy VinodDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0009-0005-1645-4597
Jeremy N BurrowsMedicines for Malaria Venture, International Center Cointrin, Route de Pré-Bois 20, 1215 Geneva, Switzerland.ORCID 0000-0001-8448-6068
Philip J RosenthalDepartment of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7953-7622
Roland A CooperDominican University of California, San Rafael, CA, USA.
Adam R RensloDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1240-2846

Funding

Research Training in Chemistry and Chemical BiologyT32GM145460 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jason E Gestwicki · 2022 to 2026
$3.1M
NIGMS NIH HHS T32 GM145460
6 · The paper itself

Abstract

For over two decades, artemisinin-based combination therapy (ACT) has been the standard of care for the treatment of uncomplicated falciparum malaria. However, artemisinin partial resistance (ART-R) is now prevalent in Southeast Asia and has emerged in eastern Africa, threatening ACT efficacy. Artefenomel, a synthetic 1,2,4-trioxolane, exhibits an extended pharmacokinetic exposure profile that predicts for efficacy against ART-R parasites. Unfortunately, the development of artefenomel was halted recently after almost a decade in the clinic. Here, we describe studies of an artefenomel-adjacent chemotype that combines potent in vitro activity against clinical ART-R parasites, an extended pharmacokinetic profile with single-exposure efficacy in a murine malaria model, and enhanced stability in human microsomes and hepatocytes. Overall, our studies reveal a heretofore underexplored trioxolane chemotype with the potential to address ART-R in a next-generation trioxolane development candidate.

Indexed as

AntimalarialsArtemisininsDrug ResistanceMalaria, FalciparumAdamantaneAnimalsDisease Models, AnimalHepatocytesHumansMiceMicrosomes, LiverPeroxidesPlasmodium falciparumAdamantaneAntimalarialsartefenomelartemisininArtemisininsPeroxides

Identifiers

PMID40779626
PMCPMC12333675

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.