Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts.
J Med Chem
; 55(11): 5591-600, 2012 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-22621623
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'-(3â³,5â³-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
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Sulfonamidas
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Neoplasias da Mama
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Inibidores da Anidrase Carbônica
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Anidrases Carbônicas
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Neoplasias Pulmonares
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Antígenos de Neoplasias
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido