Inhibition of Carbonic Anhydrase Using SLC-149: Support for a Noncatalytic Function of CAIX in Breast Cancer.

ABSTRACT: Carbonic anhydrase IX (CAIX) is considered a target for therapeutic intervention in solid tumors. In this study, the efficacy of the inhibitor, 4-(3-(2,4-difluorophenyl)-oxoimidazolidin-1-yl)benzenesulfonamide (SLC-149), is evaluated on CAIX and a CAIX-mimic. We show that SLC-149 is a better inhibitor than acetazolamide against CAIX. Binding of SLC-149 thermally stabilizes CAIX-mimic at lower concentrations compared to that of CAII. Structural examinations of SLC-149 bound to CAIX-mimic and CAII explain binding preferences. In cell culture, SLC-149 is a more effective inhibitor of CAIX activity in a triple-negative breast cancer cell line than previously studied sulfonamide inhibitors. SLC-149 is also a better inhibitor of activity in cells expressing CAIX versus CAXII. However, SLC-149 ha

SUBMITTER: Mboge MY 

PROVIDER: S-EPMC9945910 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature