Anticancer carbonic anhydrase inhibitors: a patent and literature update 2018-2022. (3rd August 2022)

• Record Type: Journal Article
• Authors: Nerella, Sridhar Goud; Singh, Priti; Arifuddin, Mohammed; Supuran, Claudiu T
• Is Part Of: Expert opinion on therapeutic patents. Volume 32:Number 8(2022)
• Page Start: 833
• Page End: 847
• Publication Date: 2022-08-03
• Subjects: Carbonic anhydrase -- isoforms hCA IX -- hCA XII -- anticancer agents -- hypoxic tumor -- inhibitor -- antibody-drug conjugate; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2022.2083502
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: Introduction: Cancer affects an increasing number of patients each year with an unacceptable death toll worldwide. A new therapeutic approach to combat tumors consists in targeting human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms IX and XII, which are tumor-associated, overexpressed enzymes in hypoxic tumors, being involved in metabolism, pH regulation, ferroptosis, and overall tumor progression. Areas covered: Small molecule hCA IX/XII and antibody drug conjugate inhibitors targeting the two enzymes and their applications in the management of cancer are discussed. Expert opinion: 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.