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We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit P. falciparum and T. gondii IMP\u03b1 functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMP\u03b1-targeting and anti-apicomplexan properties for the first time. We use circular dichroism and intrinsic tryptophan fluorescence measurements to show that moxidectin can bind directly to apicomplexan IMP\u03b1s, thereby inhibiting their key binding functions at low \u03bcM concentrations, as well as possessing anti-parasitic activity against P. falciparum in culture. The results imply a class effect in terms of IMP\u03b1\u2019s ability to be targeted by macrocyclic lactone compounds. Importantly, in the face of rising global emergence of resistance to approved anti-parasitic agents, the findings highlight the potential of moxidectin and possibly other macrocyclic lactone compounds as antimalarial agents.<\/jats:p>","DOI":"10.3390\/cells14010039","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T07:44:53Z","timestamp":1735803893000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Ivermectin Related Compound Moxidectin Can Target Apicomplexan Importin \u03b1 and Limit Growth of Malarial Parasites"],"prefix":"10.3390","volume":"14","author":[{"given":"Sujata B.","family":"Walunj","sequence":"first","affiliation":[{"name":"Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia"},{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geetanjali","family":"Mishra","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie M.","family":"Wagstaff","sequence":"additional","affiliation":[{"name":"Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-657X","authenticated-orcid":false,"given":"Swati","family":"Patankar","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory, Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-4745","authenticated-orcid":false,"given":"David A.","family":"Jans","sequence":"additional","affiliation":[{"name":"Nuclear Signaling Laboratory, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kosyna, F.K., and Depping, R. 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