{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T11:06:14Z","timestamp":1786791974103,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP220200614"],"award-info":[{"award-number":["LP220200614"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP180101085"],"award-info":[{"award-number":["LP180101085"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["AU-CH_CS-5204"],"award-info":[{"award-number":["AU-CH_CS-5204"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Phylumtech S.A.","award":["LP220200614"],"award-info":[{"award-number":["LP220200614"]}]},{"name":"Phylumtech S.A.","award":["LP180101085"],"award-info":[{"award-number":["LP180101085"]}]},{"name":"Phylumtech S.A.","award":["AU-CH_CS-5204"],"award-info":[{"award-number":["AU-CH_CS-5204"]}]},{"name":"Oz Omics Pty Ltd.","award":["LP220200614"],"award-info":[{"award-number":["LP220200614"]}]},{"name":"Oz Omics Pty Ltd.","award":["LP180101085"],"award-info":[{"award-number":["LP180101085"]}]},{"name":"Oz Omics Pty Ltd.","award":["AU-CH_CS-5204"],"award-info":[{"award-number":["AU-CH_CS-5204"]}]},{"name":"Research Internships in Science and Engineering (RISE) scholarship","award":["LP220200614"],"award-info":[{"award-number":["LP220200614"]}]},{"name":"Research Internships in Science and Engineering (RISE) scholarship","award":["LP180101085"],"award-info":[{"award-number":["LP180101085"]}]},{"name":"Research Internships in Science and Engineering (RISE) scholarship","award":["AU-CH_CS-5204"],"award-info":[{"award-number":["AU-CH_CS-5204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The control of socioeconomically important parasitic roundworms (nematodes) of animals has become challenging or ineffective due to problems associated with widespread resistance in these worms to most classes of chemotherapeutic drugs (anthelmintics) currently available. Thus, there is an urgent need to discover and develop novel compounds with unique mechanisms of action to underpin effective parasite control programmes. Here, we evaluated an in silico (computational) approach to accelerate the discovery of new anthelmintics against the parasitic nematode Haemonchus contortus (barber\u2019s pole worm) as a model system. Using a supervised machine learning workflow, we trained and assessed a multi-layer perceptron classifier on a labelled dataset of 15,000 small-molecule compounds, for which extensive bioactivity data were previously obtained for H. contortus via high-throughput screening, as well as evidence-based datasets from the peer-reviewed literature. This model achieved 83% precision and 81% recall on the class of \u2018active\u2019 compounds during testing, despite a high imbalance in the training data, with only 1% of compounds carrying this label. The trained model was then used to infer nematocidal candidates by in silico screening of 14.2 million compounds from the ZINC15 database. An experimental assessment of 10 of these candidates showed significant inhibitory effects on the motility and development of H. contortus larvae and adults in vitro, with two compounds exhibiting high potency for further exploration as lead candidates. These findings indicate that the present machine learning-based approach could accelerate the in silico prediction and prioritisation of anthelmintic small molecules for subsequent in vitro and in vivo validations.<\/jats:p>","DOI":"10.3390\/ijms26073134","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"3134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prediction and Prioritisation of Novel Anthelmintic Candidates from Public Databases Using Deep Learning and Available Bioactivity Data Sets"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-4367","authenticated-orcid":false,"given":"Aya C.","family":"Taki","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5521-4315","authenticated-orcid":false,"given":"Louis","family":"Kapp","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Institute of Cognitive Science, University of Osnabr\u00fcck, 49090 Osnabr\u00fcck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-1272","authenticated-orcid":false,"given":"Ross S.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9117-1048","authenticated-orcid":false,"given":"Brad E.","family":"Sleebs","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill C. H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-1690","authenticated-orcid":false,"given":"Robin B.","family":"Gasser","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-5467","authenticated-orcid":false,"given":"Andreas","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Max Rubner-Institut, Federal Research Institute of Nutrition and Food, 95326 Kulmbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Casulli, A. (2021). New global targets for NTDs in the WHO roadmap 2021\u20132030. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009373"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.ijpara.2021.11.001","article-title":"The yin and yang of human soil-transmitted helminth infections","volume":"51","author":"Loukas","year":"2021","journal-title":"Int. J. Parasitol."},{"key":"ref_3","unstructured":"World Health Organization (2020). Ending the Neglect to Attain the Sustainable Development Goals\u2014A Road Map for Neglected Tropical Diseases 2021\u20132030, WHO."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105103","DOI":"10.1016\/j.prevetmed.2020.105103","article-title":"Initial assessment of the economic burden of major parasitic helminth infections to the ruminant livestock industry in Europe","volume":"182","author":"Charlier","year":"2020","journal-title":"Prev. Vet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1590\/S1984-29612014042","article-title":"Reassessment of the potential economic impact of cattle parasites in Brazil","volume":"23","author":"Grisi","year":"2014","journal-title":"Rev. Bras. Parasitol. Vet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.pt.2020.09.004","article-title":"Antiparasitics in animal health: Quo vadis?","volume":"37","author":"Selzer","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_7","unstructured":"Beveridge, I., Hobbs, R., and Slapeta, J. (2015). Parasites. Australasian Animal Parasites Inside & Out, The Australian Society for Parasitology Inc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/bs.apar.2022.07.002","article-title":"Advances in diagnosis of gastrointestinal nematodes in livestock and companion animals","volume":"118","author":"Rinaldi","year":"2022","journal-title":"Adv. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.biotechadv.2013.01.008","article-title":"Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants","volume":"31","author":"Roeber","year":"2013","journal-title":"Biotechnol. Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.pt.2004.08.001","article-title":"Drug resistance in nematodes of veterinary importance: A status report","volume":"20","author":"Kaplan","year":"2004","journal-title":"Trends Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/bs.apar.2016.02.012","article-title":"Anthelmintic resistance in Haemonchus contortus: History, mechanisms and diagnosis","volume":"93","author":"Kotze","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.vetpar.2016.01.010","article-title":"Observations on the biology, epidemiology and economic relevance of rumen flukes (Paramphistomidae) in cattle kept in a temperate environment","volume":"219","author":"Sargison","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.cvfa.2019.10.001","article-title":"Helminth vaccines in ruminants: From development to application","volume":"36","author":"Claerebout","year":"2020","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/bs.apar.2016.02.011","article-title":"Immunity to Haemonchus contortus and vaccine development","volume":"93","author":"Nisbet","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ehsan, M., Hu, R.-S., Liang, Q.-L., Hou, J.-L., Song, X., Yan, R., Zhu, X.Q., and Li, X. (2020). Advances in the development of anti-Haemonchus contortus vaccines: Challenges, opportunities, and perspectives. Vaccines, 8.","DOI":"10.3390\/vaccines8030555"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1751-0813.1981.tb00451.x","article-title":"The isolation of a field strain of Haemonchus contortus in Queensland showing multiple anthelmintic resistance","volume":"57","author":"Green","year":"1981","journal-title":"Aust. Vet. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1751-0813.1979.tb15263.x","article-title":"Thiabendazole resistance in field populations of Haemonchus contortus","volume":"55","author":"Martin","year":"1979","journal-title":"Aust. Vet. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0001-706X(93)90038-D","article-title":"Molecular variation in trichostrongylid nematodes from sheep and cattle","volume":"53","year":"1993","journal-title":"Acta Trop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1186\/s13071-014-0598-z","article-title":"First report of monepantel Haemonchus contortus resistance on sheep farms in Uruguay","volume":"7","author":"Mederos","year":"2014","journal-title":"Parasit. Vectors"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1751-0813.1990.tb07390.x","article-title":"Closantel resistance in Haemonchus contortus from sheep","volume":"67","author":"Rolfe","year":"1990","journal-title":"Aust. Vet. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/bs.apar.2021.12.002","article-title":"Anthelmintic resistance in ruminants: Challenges and solutions","volume":"115","author":"Charlier","year":"2022","journal-title":"Adv. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ijpddr.2019.05.001","article-title":"Refugia and anthelmintic resistance: Concepts and challenges","volume":"10","author":"Hodgkinson","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Doyle, S.R., Tracey, A., Laing, R., Holroyd, N., Bartley, D., Bazant, W., Beasley, H., Beech, R., Britton, C., and Brooks, K. (2020). Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-01377-3"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/bs.apar.2016.02.015","article-title":"Understanding Haemonchus contortus better through genomics and transcriptomics","volume":"93","author":"Gasser","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Laing, R., Kikuchi, T., Martinelli, A., Tsai, I.J., Beech, R.N., Redman, E., Holroyd, N., Bartley, D.J., Beasley, H., and Britton, C. (2013). The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biol., 14.","DOI":"10.1186\/gb-2013-14-8-r88"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ijpddr.2017.05.004","article-title":"Screening of the \u2018Open Scaffolds\u2019 collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber\u2019s pole worm and other parasitic nematodes","volume":"7","author":"Preston","year":"2017","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1096\/fj.201700288R","article-title":"Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain","volume":"31","author":"Preston","year":"2017","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Schwarz, E.M., Korhonen, P.K., Campbell, B.E., Young, N.D., Jex, A.R., Jabbar, A., Hall, R.S., Mondal, A., Howe, A.C., and Pell, J. (2013). The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus. Genome Biol., 14.","DOI":"10.1186\/gb-2013-14-8-r89"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Taki, A.C., Byrne, J.J., Wang, T., Sleebs, B.E., Nguyen, N., Hall, R.S., Korhonen, P.K., Chang, B.C.H., Jackson, P., and Jabbar, A. (2021). High-throughput phenotypic assay to screen for anthelmintic activity on Haemonchus contortus. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070616"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103615","DOI":"10.1016\/j.jprot.2019.103615","article-title":"The developmental phosphoproteome of Haemonchus contortus","volume":"213","author":"Wang","year":"2020","journal-title":"J. Proteom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103375","DOI":"10.1016\/j.jprot.2019.05.003","article-title":"High throughput LC-MS\/MS-based proteomic analysis of excretory-secretory products from short-term in vitro culture of Haemonchus contortus","volume":"204","author":"Wang","year":"2019","journal-title":"J. Proteomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijpara.2018.12.003","article-title":"Somatic proteome of Haemonchus contortus","volume":"49","author":"Wang","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.ijpara.2018.06.002","article-title":"The developmental lipidome of Haemonchus contortus","volume":"48","author":"Wang","year":"2018","journal-title":"Int. J. Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.apar.2020.10.002","article-title":"Advances in the discovery and development of anthelmintics by harnessing natural product scaffolds","volume":"111","author":"Herath","year":"2021","journal-title":"Adv. Parasitol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apar.2019.12.003","article-title":"A perspective on the discovery of selected compounds with anthelmintic activity against the barber\u2019s pole worm\u2014Where to from here?","volume":"108","author":"Jiao","year":"2020","journal-title":"Adv. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shanley, H.T., Taki, A.C., Byrne, J.J., Jabbar, A., Wells, T.N.C., Samby, K., Boag, P.R., Nguyen, N., Sleebs, B.E., and Gasser, R.B. (2022). A high-throughput phenotypic screen of the \u2018Pandemic Response Box\u2019 identifies a quinoline derivative with significant anthelmintic activity. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020257"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Taki, A.C., Wang, T., Nguyen, N.N., Ang, C.-S., Leeming, M.G., Nie, S., Byrne, J.J., Young, N.D., Zheng, Y., and Ma, G. (2022). Thermal proteome profiling reveals Haemonchus orphan protein HCO_011565 as a target of the nematocidal small molecule UMW-868. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1014804"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrd.2017.232","article-title":"Automating drug discovery","volume":"17","author":"Schneider","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1021\/jm4004285","article-title":"QSAR modeling: Where have you been? Where are you going to?","volume":"57","author":"Cherkasov","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/minf.201000061","article-title":"Best practices for QSAR model development, validation, and exploitation","volume":"29","author":"Tropsha","year":"2010","journal-title":"Mol. Inform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.1021\/ja00226a005","article-title":"Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins","volume":"110","author":"Cramer","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1021\/ja01062a035","article-title":"p-\u03c3-\u03c0 Analysis. A method for the correlation of biological activity and chemical structure","volume":"86","author":"Hansch","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","first-page":"598","article-title":"Quantitative structure-activity relationships. VI. Non-linear dependence of biological activity on hydrophobic character: Calculation procedures for bilinear model","volume":"28","author":"Kubinyi","year":"1978","journal-title":"Arzneimittelforschung"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/jm970666c","article-title":"Can we learn to distinguish between \u201cdrug-like\u201d and \u201cnondrug-like\u201d molecules?","volume":"41","author":"Ajay","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1021\/jm980697n","article-title":"Robust QSAR models using Bayesian regularized neural networks","volume":"42","author":"Burden","year":"1999","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.taap.2014.12.014","article-title":"Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds","volume":"284","author":"Alves","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1021\/ci034160g","article-title":"Random forest: A classification and regression tool for compound classification and QSAR modeling","volume":"43","author":"Svetnik","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10785","DOI":"10.1021\/jf8022194","article-title":"Prediction of fungicidal activities of rice blast disease based on least-squares support vector machines and project pursuit regression","volume":"56","author":"Du","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D1100","DOI":"10.1093\/nar\/gkr777","article-title":"ChEMBL: A large-scale bioactivity database for drug discovery","volume":"40","author":"Gaulton","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D400","DOI":"10.1093\/nar\/gkr1132","article-title":"PubChem\u2019s BioAssay database","volume":"40","author":"Wang","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2174\/1568026614666140929120749","article-title":"Virtual screening strategies in medicinal chemistry: The state of the art and current challenges","volume":"14","author":"Braga","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1021\/acs.jcim.6b00055","article-title":"QSAR-driven discovery of novel chemical scaffolds active against Schistosoma mansoni","volume":"56","author":"Dantas","year":"2016","journal-title":"J. Chem. Inf. Model."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1021\/acs.jmedchem.5b02038","article-title":"Discovery of new anti-schistosomal hits by integration of QSAR-based virtual screening and high content screening","volume":"59","author":"Neves","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"83","DOI":"10.14573\/altex.1603091","article-title":"Making big sense from big data in toxicology by read-across","volume":"33","author":"Hartung","year":"2016","journal-title":"ALTEX"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1021\/tx500145h","article-title":"Big data in chemical toxicity research: The use of high-throughput screening assays to identify potential toxicants","volume":"27","author":"Zhu","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1007\/s11095-016-2029-7","article-title":"The next era: Deep learning in pharmaceutical research","volume":"33","author":"Ekins","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1021\/acs.jcim.7b00146","article-title":"Is multitask deep learning practical for pharma?","volume":"57","author":"Ramsundar","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/jcc.24764","article-title":"Deep learning for computational chemistry","volume":"15","author":"Goh","year":"2017","journal-title":"J. Comput. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1021\/ci500747n","article-title":"Deep neural nets as a method for quantitative structure-activity relationships","volume":"55","author":"Ma","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15\u2014Ligand discovery for everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijpddr.2016.07.004","article-title":"Screening of the \u2018Pathogen Box\u2019 identifies an approved pesticide with major anthelmintic activity against the barber\u2019s pole worm","volume":"6","author":"Preston","year":"2016","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ijpara.2015.01.007","article-title":"Low-cost whole-organism screening of compounds for anthelmintic activity","volume":"45","author":"Preston","year":"2015","journal-title":"Int. J. Parasitol."},{"key":"ref_63","unstructured":"Taki, A.C., Hall, R.S., Gasser, R.B., and Hofmann, A. (2024). Bioactivity of small-molecule compounds against Haemonchus contortus. Zenodo."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10875","DOI":"10.1021\/acs.jmedchem.8b01544","article-title":"Optimization of novel 1-methyl-1H-pyrazole-5-carboxamides leads to high potency larval development inhibitors of the barber\u2019s pole worm","volume":"61","author":"Le","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1021\/acs.jmedchem.8b01789","article-title":"Structure-activity relationship studies of tolfenpyrad reveal subnanomolar inhibitors of Haemonchus contortus development","volume":"62","author":"Le","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"112100","DOI":"10.1016\/j.ejmech.2020.112100","article-title":"Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus","volume":"190","author":"Ruan","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1021\/acs.jmedchem.8b01790","article-title":"Novel 1-methyl-1H-pyrazole-5-carboxamide derivatives with potent anthelmintic activity","volume":"62","author":"Le","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16602","DOI":"10.1002\/chem.201602851","article-title":"Organometallic derivatization of the nematocidal drug monepantel leads to promising antiparasitic drug candidates","volume":"22","author":"Hess","year":"2016","journal-title":"Chemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ijpddr.2018.12.007","article-title":"Tetrahydroquinoxalines induce a lethal evisceration phenotype in Haemonchus contortus in vitro","volume":"9","author":"Jiao","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s13071-016-1612-4","article-title":"Selenophene and thiophene-core estrogen receptor ligands that inhibit motility and development of parasitic stages of Haemonchus contortus","volume":"9","author":"Preston","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.vetpar.2019.05.008","article-title":"The antitrypanosomal diarylamidines, diminazene and pentamidine, show anthelmintic activity against Haemonchus contortus in vitro","volume":"270","author":"Nixon","year":"2019","journal-title":"Vet. Parasitol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.7164\/antibiotics.42.1593","article-title":"A novel series of milbemycin antibiotics from Streptomyces strain E225\u2014I. Discovery, fermentation and anthelmintic activity","volume":"42","author":"Hood","year":"1989","journal-title":"J. Antibiot."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpddr.2016.01.002","article-title":"In vitro anthelmintic efficacy of inhibitors of phosphoethanolamine methyltransferases in Haemonchus contortus","volume":"6","author":"Witola","year":"2016","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vetpar.2007.02.014","article-title":"In vitro and in vivo characterization of p-amino-phenethyl-m-trifluoromethylphenyl piperazine (PAPP), a novel serotonergic agonist with anthelmintic activity against Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis","volume":"146","author":"White","year":"2007","journal-title":"Vet. Parasitol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00436-010-2216-0","article-title":"Differences in efficacy of monepantel, derquantel and abamectin against multi-resistant nematodes of sheep","volume":"109","author":"Kaminsky","year":"2011","journal-title":"Parasitol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1751-0813.2003.tb11514.x","article-title":"Moxidectin-resistant Haemonchus contortus in sheep in northern New South Wales","volume":"81","author":"Love","year":"2003","journal-title":"Aust. Vet. J."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Herath, H.M.P.D., Preston, S., Jabbar, A., Garcia-Bustos, J., Taki, A.C., Addison, R.S., Hayes, S., Beattie, K.D., McGee, S.L., and Martin, S.D. (2019). Identification of fromiamycalin and halaminol A from Australian marine sponge extracts with anthelmintic activity against Haemonchus contortus. Mar. Drugs, 17.","DOI":"10.3390\/md17110598"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0304-4017(97)00065-4","article-title":"Efficacy of closantel, albendazole and levamisole on an ivermectin-resistant strain of Haemonchus contortus in sheep","volume":"73","author":"Waruiru","year":"1997","journal-title":"Vet. Parasitol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0368-1742(49)80007-5","article-title":"The anthelmintic effect of phenothiazine administered in small daily doses to lambs bearing heavy infestations of Haemonchus contortus","volume":"59","author":"Page","year":"1949","journal-title":"J. Comp. Pathol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s13071-020-04329-2","article-title":"The threat of reduced efficacy of anthelmintics against gastrointestinal nematodes in sheep from an area considered anthelmintic resistance-free","volume":"13","author":"Bosco","year":"2020","journal-title":"Parasit. Vectors"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hadipour, H., Liu, C., Davis, R., Cardona, S.T., and Hu, P. (2022). Deep clustering of small molecules at large-scale via variational autoencoder embedding and K-means. BMC Bioinform., 23.","DOI":"10.1186\/s12859-022-04667-1"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s004360100479","article-title":"Activity of the cyclic depsipeptide emodepside (BAY 44-4400) against larval and adult stages of nematodes in rodents and the influence on worm survival","volume":"87","author":"Harder","year":"2001","journal-title":"Parasitol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2005.01.013","article-title":"Tribendimidine: A promising, safe, and broad-spectrum anthelmintic agent from China","volume":"94","author":"Xiao","year":"2005","journal-title":"Acta Trop."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nature06722","article-title":"A new class of anthelmintics effective against drug-resistant nematodes","volume":"452","author":"Kaminsky","year":"2008","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.vetpar.2011.05.008","article-title":"Efficacy of a combined oral formulation of derquantel\u2013abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains","volume":"181","author":"Little","year":"2011","journal-title":"Vet. Parasitol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijpddr.2020.07.001","article-title":"Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics","volume":"14","author":"Nixon","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.3762\/bjoc.16.105","article-title":"Anthelmintic drug discovery: Target identification, screening methods, and the role of open science","volume":"16","author":"Partridge","year":"2020","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd1824","article-title":"Opportunities and challenges in antiparasitic drug discovery","volume":"4","author":"Pink","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.pt.2017.07.005","article-title":"Working towards new drugs against parasitic worms in a public-development partnership","volume":"34","author":"Preston","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ijpddr.2014.09.002","article-title":"WIPO Re:Search: Accelerating anthelmintic development through cross-sector partnerships","volume":"4","author":"Ramamoorthi","year":"2014","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Cross, M., York, M., D\u0142ugosz, E., Straub, J.H., Biberacher, S., Herath, H.M.P.D., Logan, S.A., Kim, J.S., Gasser, R.B., and Ryan, J.H. (2019). A suicide inhibitor of nematode trehalose-6-phosphate phosphatases. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-52593-9"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Knox, J., Joly, N., Linossi, E.M., Carmona-Negr\u00f3n, J.A., Jura, N., Pintard, L., Zuercher, W., and Roy, P.J. (2021). A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88150-6"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Tyagi, R., Elfawal, M.A., Wildman, S.A., Helander, J., Bulman, C.A., Sakanari, J., Rosa, B.A., Brindley, P.J., Janetka, J.W., and Aroian, R.V. (2019). Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-45548-7"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/acsinfecdis.0c00754","article-title":"A machine learning strategy for drug discovery identifies anti-schistosomal small molecules","volume":"7","author":"Zorn","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.4155\/fmc-2023-0152","article-title":"Artificial intelligence-guided approach for efficient virtual screening of hits against Schistosoma mansoni","volume":"15","author":"Neves","year":"2023","journal-title":"Future Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0020-7519(05)80009-8","article-title":"The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections","volume":"22","author":"Coyne","year":"1992","journal-title":"Int. J. Parasitol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2307\/3282218","article-title":"Size of inoculum dose regulates in part worm burdens, fecundity, and lengths in ovine Haemonchus contortus infections","volume":"74","author":"Fleming","year":"1988","journal-title":"J. Parasitol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1021\/cn300129d","article-title":"Identification of the benzyloxyphenyl pharmacophore: A structural unit that promotes sodium channel slow inactivation","volume":"3","author":"King","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7655","DOI":"10.1016\/j.bmc.2013.10.031","article-title":"Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity","volume":"21","author":"Lee","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1021\/jm100185c","article-title":"Merging the structural motifs of functionalized amino acids and \u03b1-aminoamides: Compounds with significant anticonvulsant activities","volume":"53","author":"Stables","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bmc.2017.11.036","article-title":"Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson\u2019s disease therapy","volume":"26","author":"Yeon","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.brainresbull.2020.12.018","article-title":"Safinamide in neurological disorders and beyond: Evidence from preclinical and clinical studies","volume":"168","author":"Wasan","year":"2021","journal-title":"Brain Res. Bull."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Kaji, M.D., Noonan, J.D., Geary, T.G., and Beech, R.N. (2022). Structural mechanism underlying the differential effects of ivermectin and moxidectin on the C. elegans glutamate-gated chloride channel GLC-2. Biomed. Pharmacother., 145.","DOI":"10.1016\/j.biopha.2021.112380"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"36372","DOI":"10.1074\/jbc.M403096200","article-title":"Molecular basis of the differential sensitivity of nematode and mammalian muscle to the anthelmintic agent levamisole","volume":"279","author":"Rayes","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1186\/s13071-015-1231-5","article-title":"The Haemonchus contortus kinome\u2014A resource for fundamental molecular investigations and drug discovery","volume":"8","author":"Stroehlein","year":"2015","journal-title":"Parasit. Vectors"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"100522","DOI":"10.1016\/j.ijpddr.2024.100522","article-title":"Structure-activity relationship and target investigation of 2-aryl quinolines with nematocidal activity","volume":"24","author":"Shanley","year":"2024","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_107","unstructured":"Abadi, M., Agarwal, A., Barham, P., Brevdo, E., Chen, Z., Citro, C., Corrado, G.S., Davis, A., Dean, J., and Devin, M. (2015). TensorFlow: Large-scale machine learning on heterogeneous distributed systems. arXiv."},{"key":"ref_108","unstructured":"Chollet, F. (2025, March 26). Keras. Available online: https:\/\/keras.io."},{"key":"ref_109","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"ref_110","first-page":"1929","article-title":"Dropout: A simple way to prevent neural networks from overfitting","volume":"15","author":"Srivastava","year":"2014","journal-title":"J. Mach. Learn. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13321-018-0258-y","article-title":"Mordred: A molecular descriptor calculator","volume":"10","author":"Moriwaki","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1021\/c160017a018","article-title":"The generation of a unique machine description for chemical structures\u2014A technique developed at Chemical Abstracts Service","volume":"5","author":"Morgan","year":"1965","journal-title":"J. Chem. Doc."},{"key":"ref_113","unstructured":"Kingma, D.P., and Welling, M. (2013). Auto-encoding variational Bayes. arXiv."},{"key":"ref_114","unstructured":"Sutskever, I., Martens, J., Dahl, G., and Hinton, G. (2013, January 16\u201321). On the importance of initialization and momentum in deep learning. Proceedings of the 30th International Conference on Machine Learning, Atlanta, GA, USA."},{"key":"ref_115","unstructured":"Paszke, A., Gross, S., Massa, F., Lerer, A., Bradbury, J., Chanan, G., Killeen, T., Lin, Z., Gimelshein, N., and Antiga, L. (2019, January 8). PyTorch: An imperative style, high-performance deep learning library. Proceedings of the 33rd International Conference on Neural Information Processing Systems, Red Hook, NY, USA."},{"key":"ref_116","first-page":"2579","article-title":"Visualizing data using t-SNE","volume":"9","author":"Hinton","year":"2008","journal-title":"J. Mach. Learn. Res."},{"key":"ref_117","first-page":"707","article-title":"Binary codes capable of correcting deletions, insertions, and reversals","volume":"10","author":"Levenshtein","year":"1965","journal-title":"Sov. Phys. Dokl."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13321-015-0079-1","article-title":"A practical Java tool for small-molecule compound appraisal","volume":"7","author":"Amani","year":"2015","journal-title":"J. Cheminform."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1021\/jm901137j","article-title":"New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays","volume":"53","author":"Baell","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1021\/acs.jmedchem.6b01673","article-title":"Optimization of 2-anilino 4-amino substituted quinazolines into potent antimalarial agents with oral in vivo activity","volume":"60","author":"Gilson","year":"2017","journal-title":"J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3134\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:22Z","timestamp":1760029462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":121,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073134"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073134","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}