Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts

Roben Gieling, Muhammad Babur, Lupti Mamnani, Natalie Burrows, Brian Telfer, Fabrizio Carta, Jean-Yves Winum, Andrea Scozzafava, Claudiu Supuran, Kaye Williams

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)


A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC inhibitors was generated that displayed high specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms. Three of the specific CA IX/XII inhibitors showed a positive response in in vitro assays for tumor cell migration and spreading. One of them, 4-(3′-(3″,5″-dimethylphenyl)ureido)phenyl sulfamate (S4), was taken forward into the orthotopic MDA-MB-231 (breast carcinoma) model in mice. Treatment with a 10 mg/kg maintenance dosage of S4 given daily on a “5 days on, 2 days off” regimen reduced metastatic tumor burden in the lung while not affecting primary tumor growth or mouse condition. CA inhibitors of the sulfamate class specifically targeting the tumor-associated isoforms are potential candidates in antimetastatic therapy.
Original languageEnglish
Pages (from-to)5591-55600
JournalJournal of Medicinal Chemistry
Issue number11
Publication statusPublished - 14 Jun 2012


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