![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2026\/05\/FK-Fois-Marzia-scaled-1-e1778047228993-997x1024.jpg\")
<\/figure>OC21 – Marzia Fois<\/strong><\/p>\n\n\n\n University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia<\/p>\n\n\n\n e-mail<\/a> – LinkedIn<\/a><\/strong> –<\/strong> ORCID<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n <\/p>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" OC21 – Marzia Fois University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia e-mail – LinkedIn – ORCID Targeting Mitochondrial KV1.3 in Cancer: Development of Mitochondria-Directed Inhibitors Marzia Fois1, Natalija Trunkelj1, Jaka Dernov\u0161ek1, Ma\u0161a Omerzel2, Bo\u0161tjan Markelc2, […]<\/p>\n","protected":false},"author":9643,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1715","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1715","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/9643"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=1715"}],"version-history":[{"count":7,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1715\/revisions"}],"predecessor-version":[{"id":1911,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1715\/revisions\/1911"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=1715"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=1715"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=1715"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Targeting Mitochondrial KV1.3 in Cancer: Development of Mitochondria-Directed Inhibitors<\/strong><\/td><\/tr> Marzia Fois1<\/sup>, Natalija Trunkelj1<\/sup>, Jaka Dernov\u0161ek1<\/sup>, Ma\u0161a Omerzel2<\/sup>, Bo\u0161tjan Markelc2<\/sup>, Joshua A. Nasburg3<\/sup>, Caterina Sturtzel4<\/sup>, Martin Distel4,5<\/sup>, Heike Wulff 3<\/sup>, Luis Pardo6<\/sup>, Lucija Peterlin Ma\u0161i\u010d1<\/sup>, Tihomir Toma\u0161i\u010d1<\/sup><\/em>
1<\/sup><\/em> University of Ljubljana, Faculty of Pharmacy, Askerceva cesta 7, 1000 Ljubljana, Slovenia\u00a0
2<\/sup><\/em> Oncology Institute, Department of Experimental Oncology, Zaloska cesta 2, 1000 Ljubljana, Slovenia
3<\/sup><\/em> University of California, Davis, Department of Pharmacology, 451 Health Science Drive, Davis, CA 95616, USA
4<\/sup><\/em> Children\u2019s Cancer research Institute, Zimmermannplatz 10, 1090 Wien, Austria
5<\/sup><\/em> Division of Pediatric Hematology and Oncology, Intermountain Primary Children\u2019s Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, 2000 Circle of Hope Dr., Salt Lake City, 84112, UT, USA
6<\/sup><\/em> AG Oncophysiology, Max-Planck Institute for Experimental Medicine, Hermann-Rein- Str. 3, 37075 Gottingen, Germany<\/td><\/tr>Abstract<\/strong>
The voltage-gated potassium channel KV1.3 is expressed both at the plasma membrane and in the inner mitochondrial membrane, where it plays a key role in cell proliferation and apoptosis. Mitochondrial KV1.3 (mitoKV1.3) has emerged as a promising anticancer target, although selective compartment targeting remains challenging [1]. This work focuses on the development of mitochondria-targeted KV1.3 inhibitors and the identification of a novel scaffold for plasma membrane KV1.3, providing a basis for the development of new mitochondria-targeted inhibitors. Starting from a benzamide-based scaffold [2], analogue series were designed by combining linker optimization, stereochemical modulation, and incorporation of mitochondrial targeting moieties (MTMs). Structure-activity relationship studies highlighted the importance of linker length and configuration, with five-carbon linkers and cis isomers showing improved activity. Different targeting strategies were explored, including triphenylphosphonium (TPP+), para-substituted TPP+ analogues and pyridine-based MTMs. Selected compounds displayed potent antiproliferative activity, induced mitochondrial dysfunction and apoptosis, were active in advanced models, including 3D spheroids and organoids, zebrafish xenografts, and a mouse tumour model. In parallel, ligand-based virtual screening identified a new scaffold, which was further optimized to generate new KV1.3 inhibitors and subsequently functionalized for mitochondrial targeting. Preliminary results confirmed activity, while studies on mitochondrial targeting and selectivity are currently ongoing. Overall, this work supports the combination of scaffold diversification and mitochondrial targeting as a strategy for next-generation KV1.3 anticancer agents.<\/td><\/tr>References <\/strong>
[1] Capera, J.; Navarro-P\u00e9rez, M.; Moen, A. S.; Szab\u00f3, I.; Felipe, A. The Mitochondrial Routing of the Kv1.3 Channel. Front. Oncol.<\/em> 2022<\/strong>, 12<\/em>, 865686. https:\/\/doi.org\/10.3389\/fonc.2022.865686.
[2] Gubi\u010d, \u0160.; Fois, M.; Shi, X.; D\u017eaji\u0107, I.; Secci, D.; Kolo\u0161a, K.; \u0160tern, A.; Nasburg, J. A.; Nguyen, H. M.; Carpanese, V.; Viswanathan, G.; Checchetto, V.; Omerzel, M.; Bo\u017ei\u010d, T.; Markelc, B.; Jesenko, T.; \u010cema\u017ear, M.; Szabo, I.; Wulff, H.; \u017degura, B.; Kosjek, T.; Cotman, A. E.; Toma\u0161i\u010d, T.; Pardo, L. A.; Ma\u0161i\u010d, L. P. New Mitochondrial KV<\/sub>1.3 Conjugates Are Potent and Specific Inducers of Apoptosis in Cancer Models. Biomed. Pharmacother.<\/em> 2026<\/strong>, 195<\/em>, 118996. https:\/\/doi.org\/10.1016\/j.biopha.2026.118996.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n