Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX.

ABSTRACT: We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein follow

SUBMITTER: Vaskevicius A 

PROVIDER: S-EPMC11651660 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature