ArticleThe Journal of infectious diseases2018
The Existing Drug Vorinostat as a New Lead Against Cryptosporidiosis by Targeting the Parasite Histone Deacetylases.
Article in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- A rapid sporozoite viability assay identifies leads and targetable enzymatic activities against the zoonotic Cryptosporidium parvum.International journal for parasitology. Drugs and drug resistance · 2026Article
- Profile of lysine acetylation in Eimeria tenella and its potential implications for anticoccidial research.Parasites & vectors · 2026Article
- Targeting translation initiation yields fast-killing therapeutics against the zoonotic parasite Cryptosporidium parvum.PLoS pathogens · 2025Article
- Characterization of the Activities of Vorinostat AgainstInternational journal of molecular sciences · 2025Article
- Identification of potent and orally efficacious phosphodiesterase inhibitors in Cryptosporidium parvum-infected immunocompromised male mice.Nature communications · 2024Article
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- Safe and effective treatments are needed for cryptosporidiosis, a truly neglected tropical disease.BMJ global health · 2023Article
- On-target inhibition of Cryptosporidium parvum by nitazoxanide (NTZ) and paclitaxel (PTX) validated using a novel MDR1-transgenic host cell model and algorithms to quantify the effect on the parasite target.PLoS neglected tropical diseases · 2023Article
- Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum.Microbiology spectrum · 2023Article
- Putative SET-domain methyltransferases inVirulence · 2022Article
- Activity of (1-benzyl-4-triazolyl)-indole-2-carboxamides against Toxoplasma gondii and Cryptosporidium parvum.International journal for parasitology. Drugs and drug resistance · 2022Article
- Live imaging of the Cryptosporidium parvum life cycle reveals direct development of male and female gametes from type I meronts.PLoS biology · 2022Article
- Unique Tubulin-Based Structures in the Zoonotic Apicomplexan ParasiteMicroorganisms · 2021Article
- Spontaneous Selection ofAntimicrobial agents and chemotherapy · 2021Article
- The Emerging Role of Epigenetic Mechanisms in the Causation of Aberrant MMP Activity during Human Pathologies and the Use of Medicinal Drugs.Biomolecules · 2021Review
- Article
- Nullscript inhibits Cryptosporidium and Toxoplasma growth.International journal for parasitology. Drugs and drug resistance · 2020Article
- Bicyclic azetidines kill the diarrheal pathogenScience translational medicine · 2020Article
- A Conditional Protein Degradation System To Study Essential Gene Function in Cryptosporidium parvum.mBio · 2020Article
- Novel Antiparasitic Activity of the Antifungal Lead Occidiofungin.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Background: Cryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited. Methods: An in vitro phenotypic screening assay was employed to screen 1200 existing drugs for their anticryptosporidial activity and to determine the inhibitory kinetics of top hits. Selected top hits were further evaluated in mice. The action of the lead compound vorinostat on the parasite histone deacetylase (HDAC) was biochemically validated. Results: Fifteen compounds exhibited anticryptosporidial activity at nanomolar level in vitro. Among them, the histone deacetylase (HDAC) inhibitor vorinostat retained outstanding efficacy in vitro (half maximal effective concentration, EC50 = 203 nM) and in an interleukin 12 knockout mouse model (50% inhibition dose = 7.5 mg/kg). Vorinostat was effective on various parasite developmental stages and could irreversibly kill the parasite. Vorinostat was highly effective against the parasite native HDAC enzymes (half maximal inhibitory concentration, IC50 = 90.0 nM) and a recombinant Cryptosporidium parvum HDAC (the inhibitor constant, Ki = 123.0 nM). Conclusions: These findings suggest the potential for repurposing of vorinostat to treat cryptosporidiosis, and imply that the parasite HDAC can be explored for developing more selective anticryptosporidial 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.