ArticlePLoS pathogens2013
Using existing drugs as leads for broad spectrum anthelmintics targeting protein kinases.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Anthelmintics Derived from the Kinase Inhibitor SGI-1776 for the Treatment of Gastrointestinal Worm Infections.ACS infectious diseases · 2025Article
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- Research progress and limitation analysis of RNA interference inFrontiers in veterinary science · 2023Review
- A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.Scientific reports · 2021Article
- Areas of Metabolomic Exploration for Helminth Infections.ACS infectious diseases · 2021Article
- Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control.Frontiers in endocrinology · 2021Article
- Suppression of hyaluronidase reduces invasion and establishment of Haemonchus contortus larvae in sheep.Veterinary research · 2020Article
- Article
- De novo identification of toxicants that cause irreparable damage to parasitic nematode intestinal cells.PLoS neglected tropical diseases · 2020Article
- Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics.Scientific reports · 2019Article
- Comparative genomics of the major parasitic worms.Nature genetics · 2019Article
- Probing the opportunities for designing anthelmintic leads by sub-structural topology-based QSAR modelling.Molecular diversity · 2018Article
- Identification and preliminary characterization of Hc-clec-160, a novel C-type lectin domain-containing gene of the strongylid nematode Haemonchus contortus.Parasites & vectors · 2018Article
- Improved strategy for the curation and classification of kinases, with broad applicability to other eukaryotic protein groups.Scientific reports · 2018Article
- EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development.PLoS neglected tropical diseases · 2017Article
- Article
- Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.PLoS computational biology · 2016Article
- Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option.BMC genomics · 2016Article
- Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention.Scientific reports · 2016Article
- The Haemonchus contortus kinome--a resource for fundamental molecular investigations and drug discovery.Parasites & vectors · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
As one of the largest protein families, protein kinases (PKs) regulate nearly all processes within the cell and are considered important drug targets. Much research has been conducted on inhibitors for PKs, leading to a wealth of compounds that target PKs that have potential to be lead anthelmintic drugs. Identifying compounds that have already been developed to treat neglected tropical diseases is an attractive way to obtain lead compounds inexpensively that can be developed into much needed drugs, especially for use in developing countries. In this study, PKs from nematodes, hosts, and DrugBank were identified and classified into kinase families and subfamilies. Nematode proteins were placed into orthologous groups that span the phylum Nematoda. A minimal kinome for the phylum Nematoda was identified, and properties of the minimal kinome were explored. Orthologous groups from the minimal kinome were prioritized for experimental testing based on RNAi phenotype of the Caenorhabditis elegans ortholog, transcript expression over the life-cycle and anatomic expression patterns. Compounds linked to targets in DrugBank belonging to the same kinase families and subfamilies in the minimal nematode kinome were extracted. Thirty-five compounds were tested in the non-parasitic C. elegans and active compounds progressed to testing against nematode species with different modes of parasitism, the blood-feeding Haemonchus contortus and the filarial Brugia malayi. Eighteen compounds showed efficacy in C. elegans, and six compounds also showed efficacy in at least one of the parasitic species. Hypotheses regarding the pathway the compounds may target and their molecular mechanism for activity are discussed.
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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.