ArticleCommunications biology2023
Multivariate chemogenomic screening prioritizes new macrofilaricidal leads.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- Deep phenotypic profiling uncovers cryptic effects of antifilarial drugs.PLoS pathogens · 2026Article
- Design, synthesis, and biological evaluation of a focused pyrrolo- and pyrido-quinazolinone natural products-templated library for anti-fungal and anthelmintic activities.Bioorganic & medicinal chemistry · 2026Article
- Deep phenotypic profiling uncovers cryptic effects of antifilarial drugs.bioRxiv : the preprint server for biology · 2026Article
- Nematicidal indole oxazoles and chemoattractants from soil bacteria.bioRxiv : the preprint server for biology · 2026Article
- Drug screens using the nematode Caenorhabditis elegans.Genetics · 2025Review
- Detection of a Mitochondrial Fragmentation and Integrated Stress Response Using the Cell Painting Assay.Journal of medicinal chemistry · 2024Article
- Mapping resistance-associated anthelmintic interactions in the model nematode Caenorhabditis elegans.PLoS neglected tropical diseases · 2023Article
- Phenotypic Profiling of Macrocyclic Lactones on ParasiticAntimicrobial agents and chemotherapy · 2023Article
- Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target.Antimicrobial agents and chemotherapy · 2023Article
- wrmXpress: A modular package for high-throughput image analysis of parasitic and free-living worms.PLoS neglected tropical diseases · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential. We developed a multivariate screen that identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of >50% by leveraging abundantly accessible microfilariae. Adult assays were multiplexed to thoroughly characterize compound activity across relevant parasite fitness traits, including neuromuscular control, fecundity, metabolism, and viability. Seventeen compounds from a diverse chemogenomic library elicited strong effects on at least one adult trait, with differential potency against microfilariae and adults. Our screen identified five compounds with high potency against adults but low potency or slow-acting microfilaricidal effects, at least one of which acts through a novel mechanism. We show that the use of microfilariae in a primary screen outperforms model nematode developmental assays and virtual screening of protein structures inferred with deep learning. These data provide new leads for drug development, and the high-content and multiplex assays set a new foundation for antifilarial discovery.
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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.