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.

Antimetastatic Effect of Sulfamate Carbonic Anhydrase IX Inhibitors in Breast Carcinoma Xenografts / R. G. Gieling;M. Babur;L. Mamnani;N. Burrows;B. A. Telfer;F. Carta;J. Winum;A. Scozzafava;C. T. Supuran;K. J. Williams. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 55:(2012), pp. 5591-5600. [10.1021/jm300529u]

Antimetastatic Effect of Sulfamate Carbonic Anhydrase IX Inhibitors in Breast Carcinoma Xenografts.

CARTA, FABRIZIO;SCOZZAFAVA, ANDREA;SUPURAN, CLAUDIU TRANDAFIR;
2012

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.
2012
55
5591
5600
R. G. Gieling;M. Babur;L. Mamnani;N. Burrows;B. A. Telfer;F. Carta;J. Winum;A. Scozzafava;C. T. Supuran;K. J. Williams
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/647160
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