{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:57:01Z","timestamp":1790873821272,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>\n                    To enhance the effectiveness of boron neutron capture therapy (BNCT) for advanced thyroid carcinoma (ATC), we evaluated two previously synthesized boron\u2010enriched derivatives of Lapatinib incorporating high\u2010boron clusters. Lapatinib, a tyrosine kinase inhibitor (TKI), is clinically used in targeted therapy against tumor proliferation and progression. The compounds consisted of Lapatinib\u2010pharmacophore linked either to an\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010carborane cluster (\n                    <jats:bold>Cmpd\u20101<\/jats:bold>\n                    ) or to a metallacarborane cobalta\u2010bis\u2010dicarbollide (\n                    <jats:bold>COSAN<\/jats:bold>\n                    ) anion (\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    ). In\u2009vitro studies using the ATC 8505C anaplastic thyroid carcinoma cells showed significant cellular uptake of both compounds. Neutron autoradiography revealed that\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    is located predominantly within the nucleus, suggesting that nuclear targeting may contribute to its enhanced therapeutic potential. Subsequent BNCT irradiation experiments at the Argentine nuclear reactor RA\u20103 demonstrated a marked reduction in cell survival, decreased Ki\u201067 expression, and increased apoptosis for BNCT\u2010\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    compared with BNCT using boronophenylalanine (\n                    <jats:bold>BPA<\/jats:bold>\n                    , a standard positive control), neutron\u2010alone, and control groups. In\u2009vivo studies in ATC xenografted nude mice confirmed the absence of systemic toxicity and a significant inhibition of tumor growth following\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    treatment (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01). Boron biodistribution analyses revealed favorable tumor\u2010to\u2010blood ratios (&gt;3) when\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    was combined with\n                    <jats:bold>BPA<\/jats:bold>\n                    . Overall, these results support\n                    <jats:bold>Cmpd\u20102<\/jats:bold>\n                    as a promising bimodal agent for targeted and neutron\u2010based therapy of advanced thyroid cancer.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501074","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:03:35Z","timestamp":1773687815000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nuclear\u2010Targeted Boron\u2010Lapatinib Hybrid for Enhanced Boron Neutron Capture Therapy in Advanced Thyroid Carcinoma"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2925-7347","authenticated-orcid":false,"given":"Marcos","family":"Couto","sequence":"first","affiliation":[{"name":"Grupo de Qu\u00edmica Org\u00e1nica Medicinal, Instituto de Qu\u00edmica Biol\u00f3gica Universidad de la Rep\u00fablica  Montevideo 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