Journey on VX-809-Based Hybrid Derivatives towards Drug-like F508del-CFTR Correctors: From Molecular Modeling to Chemical Synthesis and Biological Assays.

ABSTRACT: Cystic fibrosis (CF) is a genetic disease affecting the lungs and pancreas and causing progressive damage. CF is caused by mutations abolishing the function of CFTR, a protein whose role is chloride's mobilization in the epithelial cells of various organs. Recently a therapy focused on small molecules has been chosen as a main approach to contrast CF, designing and synthesizing compounds acting as misfolding (correctors) or defective channel gating (potentiators). Multi-drug therapies have been tested with different combinations of the two series of compounds. Previously, we designed and characterized two series of correctors, namely, hybrids, which were conceived including the aminoarylthiazole (AAT) core, merged with the benzodioxole carboxamide moiety featured by VX-809. In this paper,

SUBMITTER: Parodi A 

PROVIDER: S-EPMC8955485 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature