Molecular Horizons Seminar with Prof Claudiu Supuran (University of Florence, Italy.)

Carbonic anhydrases (CA, EC 4.2.1.1), are involved in many physiologic/pathologic processes connected to pH regulation, metabolism, secretion of electrolytes, diuresis, tumorigenesis (invasion and dissemination of the tumor), neuropathic pain and arthritis. Several CA inhibitors (CAIs) classes that selectively inhibit the 12 catalytically active human isoforms were unraveled in the last decade together with a general procedure for obtaining them (the tail approach). They belong to sulfonamides and isosteres, dithiocarbamates and related compounds, carboxylates and hydroxamates, coumarins, sulfocoumarin, benzoxaboroles, selenols, etc. In hyoxic tumors, alone or in combination with other agents, inhibitors targeting CA IX/XII inhibit the growth of primary tumors, the formation of metastases and deplete the cancer stem cell population, making them unique among all anticancer drugs available to date. SLC-0111, a sulfonamide CAI discovered by the author, successfully finished a Phase I clinical trial for the treatment of advanced, metastatic solid tumors in 2016. This compound is now in Phase II clinical trials, alone or in combination with other agents such as gemcitabine. 1-6 Other recent applications of CAIs and CA activators will be also discussed.