{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:44Z","timestamp":1787029244414,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"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":["LP190101209"],"award-info":[{"award-number":["LP190101209"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Parasitic nematodes cause diseases in livestock animals and major economic losses to the agricultural industry worldwide. Nematodes of the order Strongylida, including Haemonchus contortus, are particularly important. The excessive use of anthelmintic compounds to treat infections and disease has led to widespread resistance to these compounds in nematodes, such that there is a need for new anthelmintics with distinctive mechanisms of action. With a focus on discovering new anthelmintic entities, we screened 400 chemically diverse compounds within the \u2018Pandemic Response Box\u2019 (from Medicines for Malaria Venture, MMV) for activity against H. contortus and its free-living relative, Caenorhabditis elegans\u2014a model organism. Using established phenotypic assays, test compounds were evaluated in vitro for their ability to inhibit the motility and\/or development of H. contortus and C. elegans. Dose-response evaluations identified a compound, MMV1581032, that significantly the motility of H. contortus larvae (IC50 = 3.4 \u00b1 1.1 \u03bcM) and young adults of C. elegans (IC50 = 7.1 \u00b1 4.6 \u03bcM), and the development of H. contortus larvae (IC50 = 2.2 \u00b1 0.7 \u03bcM). The favourable characteristics of MMV1581032, such as suitable physicochemical properties and an efficient, cost-effective pathway to analogue synthesis, indicates a promising candidate for further evaluation as a nematocide. Future work will focus on a structure-activity relationship investigation of this chemical scaffold, a toxicity assessment of potent analogues and a mechanism\/mode of action investigation.<\/jats:p>","DOI":"10.3390\/ph15020257","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A High-Throughput Phenotypic Screen of the \u2018Pandemic Response Box\u2019 Identifies a Quinoline Derivative with Significant Anthelmintic Activity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6471-9581","authenticated-orcid":false,"given":"Harrison T.","family":"Shanley","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-4367","authenticated-orcid":false,"given":"Aya C.","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Faculty of Veterinary and Agricultural Sciences, 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, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-0046","authenticated-orcid":false,"given":"Abdul","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim N. C.","family":"Wells","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture (MMV), 1215 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirandeep","family":"Samby","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture (MMV), 1215 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-0859","authenticated-orcid":false,"given":"Peter R.","family":"Boag","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, 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":"Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, 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, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.puhe.2011.11.015","article-title":"The global burden of neglected tropical diseases","volume":"126","author":"Fenwick","year":"2012","journal-title":"Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.vetpar.2013.04.005","article-title":"Global food security: The impact of veterinary parasites and parasitologists","volume":"195","author":"Fitzpatrick","year":"2013","journal-title":"Vet. Parasitol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1756-3305-6-153","article-title":"Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance\u2014An Australian perspective","volume":"6","author":"Roeber","year":"2013","journal-title":"Parasit. Vectors"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0020-7519(94)00118-8","article-title":"Relationship of blood loss to worm numbers, biomass and egg production in Haemonchus infected sheep","volume":"25","year":"1995","journal-title":"Int. J. Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/bs.apar.2016.02.024","article-title":"Diagnosis, treatment and management of Haemonchus contortus in small ruminants","volume":"93","author":"Besier","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_7","first-page":"347","article-title":"The Anatomy and Life-History of Haemonchus contortus (Rud)","volume":"3\u20134","author":"Veglia","year":"1915","journal-title":"Rep. Dir. Vet. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.vetpar.2016.02.028","article-title":"The \u201ctoolbox\u201d of strategies for managing Haemonchus contortus in goats: What\u2019s in and what\u2019s out","volume":"220","author":"Kearney","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/bs.apar.2016.02.014","article-title":"Gaining insights into the pharmacology of anthelmintics using Haemonchus contortus as a model nematode","volume":"93","author":"Lanusse","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.vetpar.2012.03.035","article-title":"Pharmaceutical treatments of gastrointestinal nematode infections of sheep\u2014future of anthelmintic drugs","volume":"189","author":"Sargison","year":"2012","journal-title":"Vet. 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":"35","DOI":"10.1079\/AHRR200350","article-title":"Global perspectives on nematode parasite control in ruminant livestock: The need to adopt alternatives to chemotherapy, with emphasis on biological control","volume":"4","author":"Waller","year":"2003","journal-title":"Anim. Health Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.smallrumres.2016.02.021","article-title":"Keys to solving health problems in small ruminants: Anthelmintic resistance as a threat to sustainable nematode control","volume":"142","author":"Sargison","year":"2016","journal-title":"Small Rumin. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.smallrumres.2007.12.012","article-title":"Anthelmintic resistance in sheep nematodes","volume":"76","author":"Papadopoulos","year":"2008","journal-title":"Small Rumin. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00436-008-1080-7","article-title":"identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate","volume":"103","author":"Kaminsky","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2174\/1568026023393705","article-title":"Marcfortine and paraherquamide class of anthelmintics: Discovery of PNU-141962","volume":"2","author":"Lee","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/00480169.2010.67513","article-title":"Field efficacy and safety of an oral formulation of the novel combination anthelmintic, derquantel-abamectin, in sheep in New Zealand","volume":"58","author":"Little","year":"2010","journal-title":"N. Z. Vet. J."},{"key":"ref_18","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-where to from here?","volume":"108","author":"Jiao","year":"2020","journal-title":"Adv. Parasitol."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2174\/1386207317666140109120515","article-title":"Nature Bank and the Queensland compound library: Unique international resources at the Eskitis Institute for Drug Discovery","volume":"17","author":"Camp","year":"2014","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijpddr.2016.07.004","article-title":"Screening of the \u201cPathogen Box\u201d 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_22","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.vetpar.2017.07.005","article-title":"Screening of a small, well-curated natural product-based library identifies two rotenoids with potent nematocidal activity against Haemonchus contortus","volume":"244","author":"Herath","year":"2017","journal-title":"Vet. Parasitol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13071-017-2191-8","article-title":"Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus","volume":"10","author":"Jiao","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/s13071-017-2246-x","article-title":"Screening of the \u2018Stasis Box\u2019 identifies two kinase inhibitors under pharmaceutical development with activity against Haemonchus contortus","volume":"10","author":"Jiao","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ijpddr.2018.06.002","article-title":"Arylpyrrole and fipronil analogues that inhibit the motility and\/or development of Haemonchus contortus in vitro","volume":"8","author":"Herath","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13071-019-3426-7","article-title":"Phenotypic screening of the \u2018Kurz-box\u2019 of chemicals identifies two compounds (BLK127 and HBK4) with anthelmintic activity in vitro against parasitic larval stages of Haemonchus contortus","volume":"12","author":"Nguyen","year":"2019","journal-title":"Parasit. Vectors"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Taki, A.C., Brklja\u010da, R., Wang, T., Koehler, A.V., Ma, G., Danne, J., Ellis, S., Hofmann, A., Chang, B.C.H., and Jabbar, A. (2020). Natural compounds from the marine brown alga Caulocystis cephalornithos with potent in vitro-activity against the parasitic nematode Haemonchus contortus. Pathogens, 9.","DOI":"10.3390\/pathogens9070550"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Taki, A.C., Jabbar, A., Kurz, T., Lungerich, B., Ma, G., Byrne, J.J., Pflieger, M., Asfaha, Y., Fischer, F., and Chang, B.C.H. (2021). Three small molecule entities (MPK18, MPK334 and YAK308) with activity against Haemonchus contortus in vitro. Molecules, 26.","DOI":"10.3390\/molecules26092819"},{"key":"ref_31","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_32","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_33","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1021\/acs.jmedchem.8b01790","article-title":"Novel 1-methyl-1 h-pyrazole-5-carboxamide derivatives with potent anthelmintic activity","volume":"62","author":"Le","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R88","DOI":"10.1186\/gb-2013-14-8-r88","article-title":"The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery","volume":"14","author":"Laing","year":"2013","journal-title":"Genome Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1186\/gb-2013-14-8-r89","article-title":"The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus","volume":"14","author":"Schwarz","year":"2013","journal-title":"Genome Biol."},{"key":"ref_36","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_37","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. Proteom."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-020-01377-3","article-title":"Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm","volume":"3","author":"Doyle","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104500","DOI":"10.1016\/j.meegid.2020.104500","article-title":"Toward integrative \u2019omics of the barber\u2019s pole worm and related parasitic nematodes","volume":"85","author":"Ma","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/bs.apar.2019.12.005","article-title":"Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm","volume":"108","author":"Ma","year":"2020","journal-title":"Adv. Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wang, T., and Gasser, R.B. (2021). Prospects of using high-throughput proteomics to underpin the discovery of animal host\u2013nematode interactions. Pathogens, 10.","DOI":"10.3390\/pathogens10070825"},{"key":"ref_43","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_44","doi-asserted-by":"crossref","unstructured":"Holden-Dye, L., and Walker, R.J. (2014). Anthelmintic drugs and nematicides: Studies in Caenorhabditis elegans. WormBook: The Online Review of C. elegans Biology, The C. elegans Research Community.","DOI":"10.1895\/wormbook.1.143.2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ijpddr.2020.09.005","article-title":"Caenorhabditis elegans in anthelmintic research\u2014Old model, new perspectives","volume":"14","author":"Hahnel","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1002\/med.21668","article-title":"drug discovery technologies: Caenorhabditis elegans as a model for anthelmintic therapeutics","volume":"40","author":"Reguera","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_47","first-page":"D762","article-title":"WormBase: A modern model organism information resource","volume":"48","author":"Harris","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijpddr.2018.12.006","article-title":"Selected \u03b1-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro","volume":"9","author":"Herath","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.1016\/j.bmcl.2014.09.010","article-title":"Discovery of a 1,2-bis(3-indolyl)ethane that selectively inhibits the pyruvate kinase of methicillin-resistant Staphylococcus aureus over human isoforms","volume":"24","author":"Zoraghi","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17662","DOI":"10.1074\/jbc.M109.065433","article-title":"The Caenorhabditis elegans bus-2 mutant reveals a new class of O-glycans affecting bacterial resistance","volume":"285","author":"Palaima","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1124\/dmd.115.064246","article-title":"Indole and tryptophan metabolism: Endogenous and dietary routes to Ah receptor activation","volume":"43","author":"Hubbard","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1021\/acs.jmedchem.8b00147","article-title":"Nitro-group-containing drugs","volume":"62","author":"Nepali","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1021\/jm800180e","article-title":"Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (sCH 530348) with potent antiplatelet activity","volume":"51","author":"Chackalamannil","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s40268-016-0158-4","article-title":"Vorapaxar: The current role and future directions of a novel protease-activated receptor antagonist for risk reduction in atherosclerotic disease","volume":"17","author":"Gryka","year":"2017","journal-title":"Drugs R&D"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0960-894X(94)00459-S","article-title":"Chemical modification of ring C of himbacine: Discovery of a pharmacophoric element for M2-selectivity","volume":"5","author":"Malaska","year":"1995","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1016\/j.bmcl.2004.05.047","article-title":"Himbacine analogs as muscarinic receptor antagonists\u2014Effects of tether and heterocyclic variations","volume":"14","author":"Chackalamannil","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1534\/genetics.103.020230","article-title":"The GAR-3 muscarinic receptor cooperates with calcium signals to regulate muscle contraction in the Caenorhabditis elegans pharynx","volume":"167","author":"Steger","year":"2004","journal-title":"Genetics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/32160","article-title":"A molecular evolutionary framework for the phylum Nematoda","volume":"392","author":"Blaxter","year":"1998","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Smythe, A.B., Holovachov, O., and Kocot, K.M. (2019). Improved phylogenomic sampling of free-living nematodes enhances resolution of higher-level nematode phylogeny. BMC Evol. Biol., 19.","DOI":"10.1186\/s12862-019-1444-x"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9812","DOI":"10.1021\/ja962542f","article-title":"A highly efficient total synthesis of (+)-himbacine","volume":"118","author":"Chackalamannil","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1021\/jo981983+","article-title":"Total synthesis of (+)-himbacine and (+)-himbeline","volume":"64","author":"Chackalamannil","year":"1999","journal-title":"J. Org. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1021\/jm061043e","article-title":"Metabolism-identified identification of a potent thrombin receptor antagonist","volume":"50","author":"Clasby","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12977-015-0159-3","article-title":"Long lasting control of viral rebound with a new drug ABX464 targeting Rev\u2014Mediated viral RNA biogenesis","volume":"12","author":"Campos","year":"2015","journal-title":"Retrovirology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/s41598-018-37813-y","article-title":"Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing","volume":"9","author":"Vautrin","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/bs.apar.2016.02.022","article-title":"The pathophysiology, ecology and epidemiology of Haemonchus contortus infection in small ruminants","volume":"93","author":"Besier","year":"2016","journal-title":"Adv. Parasitol."},{"key":"ref_67","first-page":"37","article-title":"Quinolines and quinolones as antibacterial, antifungal, anti-virulence, antiviral and anti-parasitic agents","volume":"Volume 1282","author":"Donelli","year":"2019","journal-title":"Advances in Microbiology, Infectious Diseases and Public Health, Advances in Experimental Medicine and Biology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1042\/BJ20131214","article-title":"Cap-binding complex (CBC)","volume":"457","author":"Cowling","year":"2014","journal-title":"Biochem. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.drudis.2020.12.019","article-title":"Specific and selective induction of miR-124 in immune cells by the quinoline ABX464: A transformative therapy for inflammatory diseases","volume":"26","author":"Tazi","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_71","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_72","doi-asserted-by":"crossref","unstructured":"Rufener, L., M\u00e4ser, P., Roditi, I., and Kaminsky, R. (2009). Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000380"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1017\/S0031182013001145","article-title":"Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance","volume":"140","author":"Gilleard","year":"2013","journal-title":"Parasitology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"115174","DOI":"10.1016\/j.bmc.2019.115174","article-title":"Mass spectrometry-based cellular thermal shift assay (CETSA\u00ae) for target deconvolution in phenotypic drug discovery","volume":"28","author":"Friman","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1128\/jb.62.3.293-300.1951","article-title":"Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli","volume":"62","author":"Bertani","year":"1951","journal-title":"J. Bacteriol."},{"key":"ref_76","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_77","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_78","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_79","doi-asserted-by":"crossref","unstructured":"Stiernagle, T. (2006). Maintenance of C. elegans. WormBook: The Online Review of C. elegans Biology, The C. elegans Research Community.","DOI":"10.1895\/wormbook.1.101.1"},{"key":"ref_80","first-page":"e4019","article-title":"Basic Caenorhabditis elegans methods: Synchronization and observation","volume":"64","author":"Fontrodona","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10875","DOI":"10.1021\/acs.jmedchem.8b01544","article-title":"Optimization of novel 1-methyl-1 h-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_82","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A simple statistical parameter for use in evaluation and validation of high throughput screening assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J. Biomol. Screen."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Taki, A.C., Byrne, J.J., Boag, P.R., Jabbar, A., and Gasser, R.B. (2021). Practical high-throughput method to screen compounds for anthelmintic activity against Caenorhabditis elegans. Molecules, 26.","DOI":"10.3390\/molecules26144156"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2.20.1","DOI":"10.1002\/0471140856.tx0220s49","article-title":"Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media","volume":"49","author":"Swiss","year":"2011","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.tiv.2015.02.011","article-title":"The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death","volume":"29","author":"Kamalian","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"\u015aliwka, L., Wiktorska, K., Suchocki, P., Milczarek, M., Mielczarek, S., Lubelska, K., Cierpia\u0142, T., \u0141y\u017cwa, P., Kie\u0142basi\u0144ski, P., and Jaromin, A. (2016). The comparison of MTT and CVS assays for the assessment of anticancer agent interactions. 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