ArticleScience translational medicine2015
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
177 citing papers in PubMed, 1 synthesis or guideline pooled it, 369 citations in OpenAlex.
- Pooled it
- Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.The Lancet. Infectious diseases · 2021Trial
- Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study.The Lancet. Infectious diseases · 2018Trial
- A Randomized Trial Evaluating the Prophylactic Activity of DSM265 Against Preerythrocytic Plasmodium falciparum Infection During Controlled Human Malarial Infection by Mosquito Bites and Direct Venous Inoculation.The Journal of infectious diseases · 2018Trial
- Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study.The Lancet. Infectious diseases · 2017Trial
- DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection.The Lancet. Infectious diseases · 2017Trial
- Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.Antimicrobial agents and chemotherapy · 2016Trial
- Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.The Lancet. Infectious diseases · 2016Trial
- New thinking for the next generation of antimalarials.EMBO molecular medicine · 2026Review
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- Dual plasmepsin IX and X inhibitors are refractory to development of resistance.PLoS pathogens · 2026Article
- Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site.Cell reports · 2026Article
- Using Unbiased Chemical Proteomics Approaches to Explore the Target Landscape of the Resistance Refractory 7-Azaindole MMV022224 inACS infectious diseases · 2026Article
- ReLink-PyB: an adapted REINVENT-based framework for non-DSM PfDHODH inhibitor discovery.Scientific reports · 2026Article
- Virtual screening and molecular dynamics analysis of Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) inhibitors targeting pyrimidine biosynthesis pathway.Folia microbiologica · 2026Article
- Genetic analysis of pyrimidine biosynthetic enzymes in Plasmodium falciparum.PLoS pathogens · 2026Article
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Potent acridone antimalarial against all three life stages of Plasmodium.Nature communications · 2026Article
- Article
- A Framework for Autonomous AI-Driven Drug Discovery.bioRxiv : the preprint server for biology · 2026Article
117 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors at 13 institutions in 5 countries.
Funding
Abstract
Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy to administer drug combinations with broad-ranging activity against all manifestations of the disease. DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria. We describe studies profiling the biological activity, pharmacological and pharmacokinetic properties, and safety of DSM265, which supported its advancement to human trials. DSM265 is highly selective toward DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drug-resistant parasite isolates. Favorable pharmacokinetic properties of DSM265 are predicted to provide therapeutic concentrations for more than 8 days after a single oral dose in the range of 200 to 400 mg. DSM265 was well tolerated in repeat-dose and cardiovascular safety studies in mice and dogs, was not mutagenic, and was inactive against panels of human enzymes/receptors. The excellent safety profile, blood- and liver-stage activity, and predicted long half-life in humans position DSM265 as a new potential drug combination partner for either single-dose treatment or once-weekly chemoprevention. DSM265 has advantages over current treatment options that are dosed daily or are inactive against the parasite liver stage.
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Registered trials
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.