ArticlePLoS neglected tropical diseases2015
The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Deep Learning-Driven Anticancer Drug Discovery: Emodepside as a Potential Therapeutic Candidate for Triple-Negative Breast Cancer.Journal of chemical information and modeling · 2026Article
- Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease.Frontiers in parasitology · 2026Review
- Effects of emodepside on single-channel properties of Onchocerca volvulus SLO-1A (BK) potassium channels.Parasites & vectors · 2025Article
- Potential of emodepside for vector-borne disease control.Malaria journal · 2025Article
- Emodepside: the anthelmintic's mode of action and toxicity.Frontiers in parasitology · 2024Review
- The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration.Parasites & vectors · 2023Review
- Drug development for the treatment of onchocerciasis: Population pharmacokinetic and adverse events modeling of emodepside.PLoS neglected tropical diseases · 2022Article
- The Current Directions of Searching for Antiparasitic Drugs.Molecules (Basel, Switzerland) · 2022Review
- Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM.Nature communications · 2021Article
- Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration.PLoS pathogens · 2021Review
- Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis.PLoS pathogens · 2021Article
- Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1F3P in dogs.International journal for parasitology. Drugs and drug resistance · 2020Article
- Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections.Parasites & vectors · 2019Article
- Adverse Drug Reactions After Administration of Emodepside/Praziquantel (Profender®) in an MDR1-Mutant Australian Shepherd Dog: Case Report.Frontiers in veterinary science · 2019Article
- Onchodermatitis: Where Are We Now?Tropical medicine and infectious disease · 2018Review
- A BRIEF REVIEW ON THE MODE OF ACTION OF ANTINEMATODAL DRUGS.Acta veterinaria · 2017Article
- Research for new drugs for elimination of onchocerciasis in Africa.International journal for parasitology. Drugs and drug resistance · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anthelmintic emodepside paralyses adult filarial worms, via a mode of action distinct from previous anthelmintics and has recently garnered interest as a new treatment for onchocerciasis. Whole organism data suggest its anthelmintic action is underpinned by a selective activation of the nematode isoform of an evolutionary conserved Ca2+-activated K+ channel, SLO-1. To test this at the molecular level we compared the actions of emodepside at heterologously expressed SLO-1 alpha subunit orthologues from nematode (Caenorhabditis elegans), Drosophila melanogaster and human using whole cell voltage clamp. Intriguingly we found that emodepside modulated nematode (Ce slo-1), insect (Drosophila, Dm slo) and human (hum kcnma1)SLO channels but that there are discrete differences in the features of the modulation that are consistent with its anthelmintic efficacy. Nematode SLO-1 currents required 100 μM intracellular Ca2+ and were strongly facilitated by emodepside (100 nM; +73.0 ± 17.4%; n = 9; p < 0.001). Drosophila Slo currents on the other hand were activated by emodepside (10 μM) in the presence of 52 nM Ca2+ but were inhibited in the presence of 290 nM Ca2+ and exhibited a characteristic loss of rectification. Human Slo required 300 nM Ca2+ and emodepside transiently facilitated currents (100 nM; +33.5 ± 9%; n = 8; p<0.05) followed by a sustained inhibition (-52.6 ± 9.8%; n = 8; p < 0.001). This first cross phyla comparison of the actions of emodepside at nematode, insect and human channels provides new mechanistic insight into the compound's complex modulation of SLO channels. Consistent with whole organism behavioural studies on C. elegans, it indicates its anthelmintic action derives from a strong activation of SLO current, not observed in the human channel. These data provide an important benchmark for the wider deployment of emodepside as an anthelmintic treatment.
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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.