{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:03:36Z","timestamp":1780632216996,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The unbranched actin filaments in mammalian cells are usually composed of co\u2010polymers of a specific tropomyosin isoform with actin. Genetic manipulation has revealed that the tropomyosins largely define the functional properties of actin filaments in an isoform\u2010specific, non\u2010redundant manner. Tropomyosin isoforms play a role in human diseases including cancers, thrombocytopenia and thrombocythaemia, endometrial decidualisation resistance, and ulcerative colitis. Hence, the development of compounds that target different tropomyosins are potentially valuable tools for cell biology as well as potential therapeutics. We have recently identified compounds that target Tpm1.8\/1.9 and now address the isoform specificity of these compounds. Tpm1.8\/1.9 is primarily enriched in the lamellipodium of migrating cells but not in stress fibre bundles unlike Tpm3.1\/3.2 and Tpm4.2, which are enriched in stress fibres. Human fibroblasts also incorporate Tpm1.8\/1.9 into fine filaments emanating from the perinuclear region. Exposure of human fibroblasts and SK\u2010N\u2010SH cells to the compounds 189\u20101 and 189\u20103 results in dispersal of Tpm1.8\/1.9 from the lamellipodium and fine filaments to a diffuse organisation in the cytoplasm. In contrast, at doses that disperse Tpm1.8\/1.9, 189\u20103 has no impact on the association of either Tpm3.1\/3.2 or Tpm4.2 with actin filament bundles, whereas 189\u20101 also targets Tpm4.2. Tpm1.8\/1.9 organisation becomes dispersed between 12\u2010 and 18\u2010hour exposure to 189\u20103, and the organisation of Tpm1.8\/1.9 returns within 4\u2009h of drug washout. We conclude that the amino acid sequence differences located at 7 positions in the first 19 residues of these isoforms provide sufficient specificity to generate compounds that target Tpm1.8\/1.9 alone.<\/jats:p>","DOI":"10.1002\/cm.70055","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T13:13:41Z","timestamp":1760447621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Isoform Specificity of a Compound Targeting Actin Filaments Containing Tropomyosin Tpm1.8\/1.9"],"prefix":"10.1002","author":[{"given":"Jeff","family":"Hook","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences UNSW Sydney  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna C.","family":"Hardeman","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences UNSW Sydney  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0833-3128","authenticated-orcid":false,"given":"Peter W.","family":"Gunning","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences UNSW Sydney  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-10-0586"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200157"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.03.028"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-04-0244"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.21883"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-021-01087-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0873"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-014-9389-6"},{"key":"e_1_2_10_10_1","first-page":"511","article-title":"The Actin Cytoskeleton as a Therapeutic Target: State of the Art and Future Directions","volume":"5","author":"Giganti A.","year":"2003","journal-title":"Progress in Cell Cycle Research"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.165563"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.172502"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.10.004"},{"key":"e_1_2_10_15_1","unstructured":"Hardeman E. P.Gunning andE.Eiffe.2021.Inventors & TroBio Therapeutics Pty Ltd. assignee Sulfonamide Compounds and the Use Thereof in the Treatment of Cancer WO2021072487."},{"key":"e_1_2_10_16_1","unstructured":"Hardeman E. P.Gunning andE.Eiffe.2022.Inventors & TroBio Therapeutics Pty Ltd. assignee Substituted Indole Compounds and the Use Thereof WO2020037079A1."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47592-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E18-12-0815"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.05.034"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25136873"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90961-6"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105141"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1105\/tpc.11.6.995"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.05.053"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108280"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175862"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07599.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104484"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15081206"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/bioa.1.4.17897"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-025-00640-3"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19991001)47:1<18::AID-JEMT3>3.0.CO;2-E"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4501"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(75)85849-8"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(78)90020-7"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01267-9"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01420-y"}],"container-title":["Cytoskeleton"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.70055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cm.70055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.70055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:11:59Z","timestamp":1777356719000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cm.70055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":36,"alternative-id":["10.1002\/cm.70055"],"URL":"https:\/\/doi.org\/10.1002\/cm.70055","archive":["Portico"],"relation":{},"ISSN":["1949-3584","1949-3592"],"issn-type":[{"value":"1949-3584","type":"print"},{"value":"1949-3592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"2025-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cm.70055"}}