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

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Oncology

Background:

• Human carbonic anhydrase (hCA) isoforms IX and XII are overexpressed in hypoxic tumors.
• These enzymes play crucial roles in tumor metabolism, pH regulation, ferroptosis, and progression.
• Targeting hCA IX/XII presents a promising therapeutic strategy for cancer treatment.

Purpose of the Study:

• To review small molecule inhibitors and antibody-drug conjugates targeting hCA IX/XII.
• To discuss the applications of these inhibitors in cancer management.
• To highlight structure-based drug design opportunities for isoform-selective inhibitors.

Main Methods:

• Exploration of diverse small molecule inhibitor classes, including sulfonamides, sulfamates, and benzoxaboroles.
• Investigation of antibody-drug conjugates targeting hCA IX/XII.
• Review of patents focusing on hCA inhibitors and their combination with antitumor chemotypes.

Main Results:

• Development of various isoform-selective small molecule inhibitors based on 3D crystal structures.
• Identification of sulfonamide derivatives and hybrids as key inhibitor classes.
• SLC-0111, a sulfonamide inhibitor, is undergoing Phase Ib/II clinical trials for advanced solid tumors.

Conclusions:

• Targeting hCA IX/XII is a viable strategy for cancer therapy.
• Structure-based drug design has yielded promising isoform-selective inhibitors.
• Further clinical investigation of candidates like SLC-0111 is warranted for cancer treatment.