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

Gieling, Roben, Babur, Muhammad, Mamnani, Lupti, Burrows, Natalie, Telfer, Brian, Carta, Fabrizio, Winum, Jean-Yves, Scozzafava, Andrea, Supuran, Claudiu and Williams, Kaye (2012) Antimetastatic Effect of Sulfamate Carbonic Anhydrase IX Inhibitors in Breast Carcinoma Xenografts. Journal of Medicinal Chemistry, 55 (11). pp. 5591-5600. ISSN 0022-2623

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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.

Item Type:	Article
Subjects:	B900 Others in Subjects allied to Medicine F100 Chemistry
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Becky Skoyles
Date Deposited:	10 Jul 2018 11:44
Last Modified:	11 Oct 2019 20:00
URI:	http://nrl.northumbria.ac.uk/id/eprint/34901

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