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

112 Citations (Scopus)

Abstract

A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC 4.2.1.1) 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
Volume55
Issue number11
DOIs
Publication statusPublished - 14 Jun 2012

Fingerprint

Dive into the research topics of 'Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts'. Together they form a unique fingerprint.

Cite this