Anticancer carbonic anhydrase inhibitors: a patent and literature update 2018-2022.

The available 3D crystal structures of hCA IX, XII as well as the off target isoforms hCA I and II, afforded structure-based drug design opportunities, which led to the development of various isoform-selective small molecule inhibitors belonging to diverse classes (sulfonamides, sulfamates, benzoxaboroles, selenols, coumarins, sulfocoumarins, and isocoumarins). Many patents focused on small inhibitors containing sulfonamide/sulfamide/sulfamide derivatives as well as hybrids incorporating sulfonamides and different antitumor chemotypes, such as cytotoxic drugs, kinase/telomerase inhibitors, P-gp and thioredoxin inhibitors. The most investigated candidate belonging to the class is the sulfonamide SLC-0111, in Phase Ib/II clinical trials for the management of advanced, metastatic solid tumors.