Carbonic Anhydrase IX as a Target for Designing Novel Anticancer Drugs

S.      M. Monti; C.      T. Supuran; G.      De Simone

Abstract

Carbonic anhydrase IX (CA IX) is a tumor associated protein, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. It is a multi-domain protein consisting of an N-terminal proteoglycan-like (PG) domain, a catalytic domain, a trans-membrane portion (TM) and an intracytoplasmatic (IC) segment. These domains have peculiar biochemical and physiological features. Among these, only the PG domain is unique among the CA family. This review focuses on the most recent molecular and catalytic features uncovered of this enzyme, the role of its different domains in tumor physiology, and its three dimensional structure which has recently been solved. In addition, we present recent advances in the development of antibodies and small inhibiting molecules able to target CA IX for diagnostic and therapeutic applications.

Keywords: Anti-tumor drugs, carbonic anhydrase IX, inhibitors, monoclonal antibody, structure based drug design, Carbonic anhydrase, tumor, intracytoplasmatic, enzyme, carcinomas