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Available treatments are typically narrow spectrum and are complicated by drug toxicity and the development of resistant parasites. Protozoan tubulin is an attractive target for the development of broad\u2010spectrum antimitotic agents. The Medicines for Malaria Pathogen Box compound MMV676477 was previously shown to inhibit replication of kinetoplastid parasites, such as <jats:italic>Leishmania amazonensis<\/jats:italic> and <jats:italic>Trypanosoma brucei<\/jats:italic>, and the apicomplexan parasite <jats:italic>Plasmodium falciparum<\/jats:italic> by selectively stabilizing protozoan microtubules. In this report, we show that MMV676477 inhibits intracellular growth of the human apicomplexan pathogen <jats:italic>Toxoplasma gondii<\/jats:italic> with an EC<jats:sub>50<\/jats:sub> value of ~50\u2009nM. MMV676477 does not stabilize vertebrate microtubules or cause other toxic effects in human fibroblasts. The availability of tools for genetic studies makes <jats:italic>Toxoplasma<\/jats:italic> a useful model for studies of the cytoskeleton. We conducted a forward genetics screen for MMV676477 resistance, anticipating that missense mutations would delineate the binding site on protozoan tubulin. Unfortunately, we were unable to use genetics to dissect target interactions because no resistant parasites emerged. This outcome suggests that future drugs based on the MMV676477 scaffold would be less likely to be undermined by the emergence of drug resistance.<\/jats:p>","DOI":"10.1002\/cm.21876","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T06:55:00Z","timestamp":1715928900000},"page":"5-11","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Toxoplasma<\/i> replication is inhibited by <scp>MMV676477<\/scp> without development of resistance"],"prefix":"10.1002","volume":"82","author":[{"given":"Izra","family":"Abbaali","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn M.","family":"Wetzel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Biochemistry University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8810-3543","authenticated-orcid":false,"given":"Naomi S.","family":"Morrissette","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010068"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c00729"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S60973"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab929"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767130-00015"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.913809"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V92155"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.148"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2392684"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(84)90515-x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00154"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.113"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013818"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-4-2"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-16765-4"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0722"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30283-3"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-6851(01)00212-2"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(88)90014-9"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-11-0634"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-777X.62883"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11030706"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-07-0530"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.5.1017"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202100273"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908239116"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01249-7"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.691121"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00298"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2567-0"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jeu.12951"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.05.001"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1996.0124"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20100025"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00122"},{"issue":"2","key":"e_1_2_5_37_1","first-page":"184","article-title":"Influence of taxol on the response of platelets to chilling","volume":"108","author":"White J. 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