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{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T10:07:33Z","timestamp":1699524453299},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of ATP\u2010binding cassette (ABC) transporter\u2010mediated multidrug resistance (MDR) in anti\u2010cancer therapy is often challenging, frequently leading to inefficiency of treatments. Cancer cells exploit efflux transporters, like the breast cancer resistance protein (BCRP, ABCG2), to secrete chemotherapeutic substances. In this study, an <jats:italic>N<\/jats:italic>\u2010phenyl\u20102\u2010carboranylquinazolin\u20104\u2010amine (<jats:bold>8<\/jats:bold>) was designed as inorganic\u2010organic hybrid BCRP inhibitor. In particular, the ABCG2\u2010transporter inhibitor\u2010prominent scaffold <jats:italic>N<\/jats:italic>\u2010phenylquinazolin\u20104\u2010amine was combined with a boron\u2212carbon cluster (carborane) moiety. Introducing a carborane at 2\u2010position of the quinazoline scaffold resulted in an increased inhibitory activity towards human ABCG2 (hABCG2) compared to its recently published regioisomer <jats:italic>N<\/jats:italic>\u2010carboranyl\u20102\u2010phenyl\u2010quinazolin\u20104\u2010amine. The carboranylquinazoline <jats:bold>8<\/jats:bold> further showed the ability to reverse hABCG2\u2010mediated drug resistance in MDCKII\u2010hABCG2 cells by lowering the IC<jats:sub>50<\/jats:sub> value of the BCRP\u2010substrate mitoxantrone, similar to the standard reference and strong inhibitor Ko143, without exhibiting intrinsic toxicity in the lower micromolar ranges. These results make compound <jats:bold>8<\/jats:bold> a promising scaffold for the design of further BCRP inhibitors.<\/jats:p>","DOI":"10.1002\/cmdc.202300094","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T12:35:52Z","timestamp":1680093352000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["2\u2010Carboranylquinazoline: The Path to an ABCG2 Inhibitor"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"http:\/\/orcid.org\/0000-0002-4174-8539","authenticated-orcid":false,"given":"Philipp","family":"Stockmann","sequence":"first","affiliation":[{"name":"Institute of Inorganic Chemistry Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig Johannisallee 29 04103 Leipzig Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-9779-2440","authenticated-orcid":false,"given":"Lydia","family":"Kuhnert","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Pharmacy and Toxicology Faculty of Veterinary Medicine Universit\u00e4t Leipzig An den Tierkliniken 15 04103 Leipzig Germany"}]},{"given":"Lisa","family":"Z\u00f6rner","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig Johannisallee 29 04103 Leipzig Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-5954-0659","authenticated-orcid":false,"given":"Walther","family":"Honscha","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology Pharmacy and Toxicology Faculty of Veterinary Medicine Universit\u00e4t Leipzig An den Tierkliniken 15 04103 Leipzig Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0003-4267-0603","authenticated-orcid":false,"given":"Evamarie","family":"Hey\u2010Hawkins","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry Faculty of Chemistry and Mineralogy Universit\u00e4t Leipzig Johannisallee 29 04103 Leipzig Germany"}]}],"m
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