Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.

ABSTRACT: The past two decades have witnessed major breakthroughs in developing compounds that target the chloride channel CFTR for the treatment of patients with cystic fibrosis. However, further improvement in affinity and efficacy for these CFTR modulators will require insights into the molecular interactions between CFTR modulators and their binding targets. In this study, we use in silico molecular docking to identify potential binding sites for GLPG1837, a CFTR potentiator that may share a common mechanism and binding site with VX-770, the FDA-approved drug for patients carrying mutations with gating defects. Among the five binding sites predicted by docking, the two top-scoring sites are located at the interface between CFTR's two transmembrane domains: site I consists of D924, N1138, and S11

SUBMITTER: Yeh HI 

PROVIDER: S-EPMC6605684 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature