Carbonic anhydrase inhibitors: The first selective, membrane-impermeant inhibitors targeting the tumor-associated isozyme IX

Pastorekova, S, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542, Scozzafava, A, Vullo, D, Pastorek, J and Supuran, CT 2004. Carbonic anhydrase inhibitors: The first selective, membrane-impermeant inhibitors targeting the tumor-associated isozyme IX. Bioorganic and Medicinal Chemistry Letters 14 (4) , pp. 869-873. 10.1016/j.bmcl.2003.12.029

Full text not available from this repository.

Abstract

The inhibition of the tumor-associated transmembrane carbonic anhydrase IX (CA IX) isozyme possessing an extracellular active site has been investigated with a series of positively-charged, pyridinium derivatives of sulfanilamide, homosulfanilamide and 4-aminoethylbenzenesulfonamide. Inhibition data for the physiologically relevant isozymes I and II (cytosolic forms) and IV (membrane-bound) were also provided for comparison. A very interesting inhibition profile against CA IX with these sulfonamides has been observed. Several nanomolar (Ki's in the range of 6–54 nM) CA IX inhibitors have also been detected. Because CA IX is a highly active isozyme predominantly expressed in tumor tissues with bad prognosis of disease progression, this finding is very promising for the potential design of CA IX-specific inhibitors with applications as anti-tumor agents. This is the first report of inhibitors that may selectively target CA IX, due to their membrane-impermeability and high affinity for this clinically relevant isozyme.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology
Publisher:	Elsevier
ISSN:	0960-894X
Last Modified:	31 Oct 2022 10:38
URI:	https://orca.cardiff.ac.uk/id/eprint/85535

Citation Data

Cited 141 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item