Abstract
Carbonic anhydrases (CAs; EC 4.2.1.1) are well known zinc metalloproteins involved in the catalysis of a very simple but essential physiological reaction: carbon dioxide hydration to bicarbonate and proton. These enzymes are of clinical relevance in cancer therapy as among the 15 isoforms known in humans, two cell surface CA isoforms, namely CA IX (almost exclusively associated with tumors) and CA XII (overexpressed in some tumor types) are involved in tumorigenesis. Targeting the tumor associated isoforms IX is now considered as a pertinent approach for the development of new cancer therapeutics against hypoxic tumors. Different approaches and new family of pharmacological agents were described in the last 5 years for obtaining compounds that specifically target CA IX over the ubiquitous cytosolic off-target isoforms CA I and CA II. The aim of this review is to give a comprehensive update on the reported discoveries in the field of CA IX inhibitors with an emphasis on the new families of compounds which reach in vivo/preclinical studies for their potential in cancer therapy.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.