Advances in Anthelmintic Target Identification

Shanley, HT; Wang, T; Taki, AC; Byrne, JJ; Chang, BCH; Sleebs, BE; Gasser, RB

Author(s): Shanley, HT; Wang, T; Taki, AC; Byrne, JJ; Chang, BCH; Sleebs, BE; Gasser, RB;
Details: Publication Year 2025-04-15,Volume 26,Issue #8,Page 3738
Journal Title: International Journal of Molecular Sciences
Abstract: Parasitic nematodes pose a significant threat to human and animal health, causing widespread morbidity and substantial socioeconomic losses globally. Despite the utility of anthelmintic drugs in parasite control, the emergence of widespread resistance necessitates the discovery of novel interventions. Advances through the use of whole-organism phenotypic screening have identified some promising nematocidal compounds, including nemacol, tolfenpyrad, UMW-9729, and ABX464. This article summarises efforts in this discovery, with a focus on Haemonchus contortus and Caenorhabditis elegans as model nematodes, and discusses approaches used for drug target deconvolution, including proteomic, chemical and genetic/genomic techniques. Stability-based proteomic assays, such as thermal proteome profiling, have been useful for identifying protein targets for these compounds, shedding light on their mechanisms of action. However, challenges remain in extrapolating findings from C. elegans to parasitic nematodes, emphasising the need for validation studies. Understanding drug-target interactions in nematodes is critical for developing next-generation anthelmintics and for mitigating the growing resistance challenge. This review outlines recent progress in this area and discusses future directions in target validation and anthelmintic development to support parasite control programmes.
Publisher: MDPI
Keywords: Animals; *Anthelmintics/pharmacology/therapeutic use; Caenorhabditis elegans/drug effects/genetics; Haemonchus/drug effects/genetics; Proteomics/methods; Humans; Drug Discovery/methods; Drug Resistance; Nematoda/drug effects; Caenorhabditis elegans; Haemonchus contortus; anthelmintic target identification; nematocide
Research Division(s): New Medicines and Diagnostics
PubMed ID: 40332360
Publisher's Version: https://doi.org/10.3390/ijms26083738
Open Access at Publisher's Site: https://doi.org/10.3390/ijms26083738
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: ijms-26-03738-v2.pdf - (0.92MB, application/pdf)

Creation Date: 2025-05-29 02:03:18

Last Modified: 2025-05-29 02:27:41