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

Roben G. Gieling; Muhammad Babur; Lupti Mamnani; Natalie Burrows; Brian A. Telfer; Fabrizio Carta; Jean Yves Winum; Andrea Scozzafava; Claudiu T. Supuran; Kaye J. Williams

doi:10.1021/jm300529u

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

Roben G. Gieling, Muhammad Babur, Lupti Mamnani, Natalie Burrows, Brian A. Telfer, Fabrizio Carta, Jean Yves Winum, Andrea Scozzafava, Claudiu T. Supuran, Kaye J. Williams

Research output: Contribution to journal › Article › peer-review

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 American Chemical Society.

Original language	English
Pages (from-to)	5591-5600
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	11
DOIs	https://doi.org/10.1021/jm300529u
Publication status	Published - 14 Jun 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/jm300529u

Cite this

@article{118b91e402fa472bbd1ba109f83a2163,

title = "Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts",

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. {\textcopyright} 2012 American Chemical Society.",

author = "Gieling, {Roben G.} and Muhammad Babur and Lupti Mamnani and Natalie Burrows and Telfer, {Brian A.} and Fabrizio Carta and Winum, {Jean Yves} and Andrea Scozzafava and Supuran, {Claudiu T.} and Williams, {Kaye J.}",

note = ", Biotechnology and Biological Sciences Research Council, United Kingdom, Wellcome Trust, United Kingdom",

year = "2012",

month = jun,

day = "14",

doi = "10.1021/jm300529u",

language = "English",

volume = "55",

pages = "5591--5600",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "11",

}

TY - JOUR

T1 - Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts

AU - Gieling, Roben G.

AU - Babur, Muhammad

AU - Mamnani, Lupti

AU - Burrows, Natalie

AU - Telfer, Brian A.

AU - Carta, Fabrizio

AU - Winum, Jean Yves

AU - Scozzafava, Andrea

AU - Supuran, Claudiu T.

AU - Williams, Kaye J.

N1 - , Biotechnology and Biological Sciences Research Council, United Kingdom, Wellcome Trust, United Kingdom

PY - 2012/6/14

Y1 - 2012/6/14

N2 - 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 American Chemical Society.

AB - 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 American Chemical Society.

U2 - 10.1021/jm300529u

DO - 10.1021/jm300529u

M3 - Article

C2 - 22621623

SN - 0022-2623

VL - 55

SP - 5591

EP - 5600

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 11

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this