Claudiu T. Supuran is professor of medicinal and pharmaceutical chemistry at the University of Florence, Italy, since 1995. He was a visiting scholar at University of Florida, Gainesville, USA, at Grifitth University, Brisbane, Australia, and visiting professor at University of La Plata, Argentina, at Federal University of Rio de Janeiro, Brazil, and at UNSW, Sydney, Australia (several times). His research is in the medicinal chemistry/biochemistry of metalloenzymes, mainly carbonic anhydrases, field in which he has made contributions to the design of many novel classes of enzyme inhibitors and activators, deciphering their mechanism of action at molecular level, discovery of new isoforms and their role in disease (cancer, obesity, epilepsy, neuropathic pain and cognition), discovery and characterization of carbonic anhydrases from various organisms (bacteria, fungi, protozoans, sponges, corals, plants, diatoms, vertebrates, etc). Other research interests include X-ray crystallography of metallo-enzymes, heterocyclic chemistry, chemistry of sulfonamides, sulfamates and sulfamides, biologically active organo-element derivatives, metal-based drugs, cyclooxygenases, serine proteases, matrix metalloproteinases, bacterial proteases, and computational chemistry. He has published more than 1900 papers in these fields and his Hirsch index is 155, with > 106198 citations. One of the compounds discovered in his laboratory (SLC-0111) is in Phase II clinical trials for the treatment of advanced metastatic solid tumors in Canada/USA, whereas a monoclonal antibody of which he is co-discoverer (6A10) is in preclinical evaluation and anti-tumor theragnotic agent.
Carbonic anhydrase (CA, EC 184.108.40.206) isoforms IX and XII are overexpressed in many hypoxic tumors as a consequence of the hypoxia inducible factor (HIF) activation cascade, being present in limited amounts in normal tissues. These enzymes together with many others are involved in the pH regulation and metabolism of hypoxic cancer cells, and were validated as antitumor targets recently, both for treatment and imaging. A multitude of targeting strategies against these enzymes have been proposed. The small molecule inhibitors, small molecule drug conjugates (SMDCs), antibody-drug conjugates (ADCs) or cytokine-drug conjugates and several monoclonal antibodies against CA IX/XII will be discussed. Relevant synthetic chemistry efforts, coupled with a multitude of preclinical studies, demonstrated that CA IX/XII inhibition leads to the inhibition of growth of primary tumors and metastases and depletes cancer stem cell populations, all factors highly relevant in clinical settings. One small molecule inhibitor, sulfonamide SLC-0111 discovered in the author’s laboratory, is the most advanced candidate, having completed Phase I and being now in Phase Ib/II clinical trials for the treatment of advanced hypoxic, metastatic solid tumors [1-4].
1. Supuran CT. Carbonic anhydrase inhibitors: an update on experimental agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs. 2021;30(12):1197-1208.
2. Mussi S, Rezzola S, Chiodelli P, Nocentini A, Supuran CT, Ronca R. Antiproliferative effects of sulphonamide carbonic anhydrase inhibitors C18, SLC-0111 and acetazolamide on bladder, glioblastoma and pancreatic cancer cell lines. J Enzyme Inhib Med Chem. 2022;37(1):280-286.
3. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nature Rev Drug Discov. 2011;10(10):767-77.
4. Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nature Rev Drug Discov. 2008;7(2):168-81