ArticleACS infectious diseases2018
Identification of Collateral Sensitivity to Dihydroorotate Dehydrogenase Inhibitors in Plasmodium falciparum.
Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Virtual screening and molecular dynamics analysis of Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) inhibitors targeting pyrimidine biosynthesis pathway.Folia microbiologica · 2026Article
- Evolutionary drivers of divergent collateral sensitivity responses during antibiotic therapy.Nature ecology & evolution · 2026Review
- Article
- The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis.Nature communications · 2023Article
- Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation.Nature communications · 2023Article
- Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance.PLoS pathogens · 2022Article
- Re-Envisioning Anti-Apicomplexan Parasite Drug Discovery Approaches.Frontiers in cellular and infection microbiology · 2021Review
- Lead Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series for the Treatment of Malaria.Journal of medicinal chemistry · 2020Article
- In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model.Science translational medicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Drug resistance has been reported for every antimalarial in use highlighting the need for new strategies to protect the efficacy of therapeutics in development. We have previously shown that resistance can be suppressed with a population biology trap: by identifying situations where resistance to one compound confers hypersensitivity to another (collateral sensitivity), we can design combination therapies that not only kill the parasite but also guide its evolution away from resistance. We applied this concept to the Plasmodium falciparum dihydroorotate dehydrogenase ( PfDHODH) enzyme, a well validated antimalarial target with inhibitors in the development pipeline. Here, we report a high-throughput screen to identify compounds specifically active against PfDHODH resistant mutants. We additionally perform extensive cross-resistance profiling allowing us to identify compound pairs demonstrating the potential for mutually incompatible resistance. These combinations represent promising starting points for exploiting collateral sensitivity to extend the useful lifespan of new antimalarial therapeutics.
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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.