Probing Allosteric Hsp70 Inhibitors by Molecular Modelling Studies to Expedite the Development of Novel Combined F508del CFTR Modulators.

ABSTRACT: Cystic fibrosis (CF) is caused by different mutations related to the cystic fibrosis transmembrane regulator protein (CFTR), with F508del being the most common. Pioneering the development of CFTR modulators, thanks to the development of effective correctors or potentiators, more recent studies deeply encouraged the administration of triple combination therapeutics. However, combinations of molecules interacting with other proteins involved in functionality of the CFTR channel recently arose as a promising approach to address a large rescue of F508del-CFTR. In this context, the design of compounds properly targeting the molecular chaperone Hsp70, such as the allosteric inhibitor MKT-077, proved to be effective for the development of indirect CFTR modulators, endowed with ability to amplify

SUBMITTER: Sabbadini R 

PROVIDER: S-EPMC8709398 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature