![\"\"](\"http:\/\/sites.unica.it\/pe2026\/files\/2025\/09\/cropped-00_Profile_Tondo-Social__Spilla_PE26_1200px.png\")
<\/figure>PC36 – Barbora Svobodova<\/strong><\/p>\n\n\n\n Biomedical Research Centre, University Hospital Hradec Kralove, Czech Republic<\/p>\n\n\n\n barbora.svobodova@fnhk.cz<\/strong><\/p>\n<\/div><\/div>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" PC36 – Barbora Svobodova Biomedical Research Centre, University Hospital Hradec Kralove, Czech Republic barbora.svobodova@fnhk.cz A Novel FLT3-Targeted Strategy to Overcome Drug Resistance in Acute Myeloid Leukemia Svobodova Barbora1, Lukas Gorecki1, Jan Korabecny1,Martina Ceckova2, Martina Rezacova3 1 […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2112","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2112","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\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2112"}],"version-history":[{"count":3,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2112\/revisions"}],"predecessor-version":[{"id":2360,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2112\/revisions\/2360"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2112"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2112"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2112"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}A Novel FLT3-Targeted Strategy to Overcome Drug Resistance in Acute Myeloid Leukemia<\/strong><\/strong><\/strong><\/td><\/tr> Svobodova Barbora1<\/sup>, Lukas Gorecki1<\/sup>, Jan Korabecny1<\/sup>,Martina Ceckova2<\/sup>, Martina Rezacova3<\/sup><\/em>
1<\/sup><\/em> Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
2<\/sup><\/em> Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic
3<\/sup><\/em> Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic<\/td><\/tr>Abstract<\/strong>
Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy associated with poor therapeutic responses and low cure rates [1]. Despite significant advances in targeted treatment strategies, clinical outcomes for many patients remain unsatisfactory [2]. Among the molecular abnormalities implicated in AML pathogenesis, mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are particularly prevalent, occurring in approximately 30% of cases and constituting a major therapeutic target. Although FLT3 inhibitors such as midostaurin and gilteritinib have entered clinical practice, the rapid development of resistance severely limits their long-term efficacy, underscoring the urgent need for novel FLT3-directed therapies [3]. Through comprehensive kinase screening, we identified a small-molecule compound, K1872, which exhibits unique structural characteristics and a pharmacophore distinct from currently available FLT3 inhibitors. Molecular dynamics simulations suggest that K1872 may effectively circumvent resistance mechanisms commonly associated with existing FLT3-targeted agents. Ongoing hit-to-lead and lead-optimization efforts are focused on evaluating the anti-proliferative and pro-apoptotic effects of K1872 derivatives in AML cell lines and patient-derived samples. Preliminary results demonstrate superior activity of K1872-related compounds in FLT3-mutated AML cells, particularly through robust induction of apoptosis, together with selective inhibition of FLT3 kinase activity. Collectively, these findings identify K1872 derivatives as promising candidates for overcoming FLT3 inhibitor resistance and improving therapeutic outcomes in AML.<\/td><\/tr>References <\/strong>
[1] A.C. Przespolewski, E.A. Griffiths, FLT3-mutated acute myeloid leukaemia: a new opportunity, Lancet 401 <\/em>(2023<\/strong>) 1546\u20131548. https:\/\/doi.org\/10.1016\/S0140-6736(23)00617-7.
[2] J.C. Zhao, S. Agarwal, H. Ahmad, K. Amin, J.P. Bewersdorf, A.M. Zeidan, A review of FLT3 inhibitors in acute myeloid leukemia, Blood Rev<\/em> 52 (2022<\/strong>) 100905. https:\/\/doi.org\/10.1016\/j.blre.2021.100905.
[3] A.K. Abdel-Aziz, E.M.E. Dokla, M.K. Saadeldin, FLT3 inhibitors and novel therapeutic strategies to reverse AML resistance: An updated comprehensive review, Crit Rev Oncol Hematol<\/em> 191 (2023<\/strong>) 104139. https:\/\/doi.org\/10.1016\/j.critrevonc.2023.104139.
The study was funded by the Czech Health Research Council, project No. NU23-08-00439<\/em>.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n