ArticlePLoS neglected tropical diseases2015
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni.
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 41 papers.
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Who cites it
41 citing papers in PubMed.
- Onchocerciasis Drug Discovery: In Vitro Evaluation of FDA-Approved Drugs againstPharmaceutics · 2024Article
- A drug repurposing screen for whipworms informed by comparative genomics.PLoS neglected tropical diseases · 2023Article
- Plumbagin: A Promising In Vivo Antiparasitic Candidate againstBiomedicines · 2023Article
- Phenotypic Profiling of Macrocyclic Lactones on ParasiticAntimicrobial agents and chemotherapy · 2023Article
- Prevalence of Intestinal Helminth Coinfection in Drug-Resistant Tuberculosis in Uganda.Open forum infectious diseases · 2022Article
- Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries.iScience · 2022Article
- The Pandemic Response Box─Accelerating Drug Discovery Efforts after Disease Outbreaks.ACS infectious diseases · 2022Article
- Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis.Parasites & vectors · 2021Article
- Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection.Antimicrobial agents and chemotherapy · 2021Article
- High-content approaches to anthelmintic drug screening.Trends in parasitology · 2021Review
- Evaluation of Human Liver Microtissues for Drug Screening onACS infectious diseases · 2021Article
- Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma.PLoS neglected tropical diseases · 2021Article
- Identification of hit compounds with anti-schistosomal activity on in vitro generated juvenile worms in cell-free medium.PLoS neglected tropical diseases · 2021Article
- Validation of a human-serum-based in vitro growth method for drug screening on juvenile development stages of Schistosoma mansoni.PLoS neglected tropical diseases · 2021Article
- A Machine Learning Strategy for Drug Discovery Identifies Anti-Schistosomal Small Molecules.ACS infectious diseases · 2021Article
- Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.Frontiers in immunology · 2021Review
- A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.Communications biology · 2020Article
- Efficacy, metabolism and pharmacokinetics of Ro 15-5458, a forgotten schistosomicidal 9-acridanone hydrazone.The Journal of antimicrobial chemotherapy · 2020Article
- Identification of annotated bioactive molecules that impair motility of the blood fluke Schistosoma mansoni.International journal for parasitology. Drugs and drug resistance · 2020Article
- Parallelized Impedance-Based Platform for Continuous Dose-Response Characterization of Antischistosomal Drugs.Advanced biosystems · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel antischistosomal leads. METHODOLOGY: 1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration of 10 µM. Active compounds identified from this screen were advanced to the adult worm screen at 33.33 µM, followed by hit characterization. Leads with complementary pharmacokinetic and toxicity profiles were then selected for in vivo studies. PRINCIPAL
findingsThe in vitro screen identified 121 and 36 compounds active against the schistosomula and adult stage, respectively. Further, in vitro characterization and comparison with already available pharmacokinetic and toxicity data identified 11 in vivo candidates. Doramectin (10 mg/kg) and clofazimine (400 mg/kg) were found to be active in vivo with worm burden reductions of 60.1% and 82.7%, respectively. CONCLUSIONS/SIGNIFICANCE: The work presented here expands the knowledge of antischistosomal properties of already approved compounds and underscores variations observed between target-based and phenotypic approaches and among laboratories. The two in vivo-active drugs identified in this study, doramectin and clofazimine are widely available and present as novel drug classes as starting points for further investigation.
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