In silico drug repositioning on F508del-CFTR: A proof-of-concept study on the AIFA library

Eur J Med Chem. 2021 Mar 5;213:113186. doi: 10.1016/j.ejmech.2021.113186. Epub 2021 Jan 13.


Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cystic fibrosis (CF), a disease mainly caused by deletion of Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. F508del-CFTR is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. CF is still a fatal disease. Nowadays, it is treatable by some CFTR-rescuing drugs, but new-generation drugs with stronger therapeutic benefits and fewer side effects are still awaited. In this manuscript we report about the results of a pilot computational drug repositioning screening in search of F508del-CFTR-targeted drugs performed on AIFA library by means of a dedicated computational pipeline and surface plasmon resonance binding assay to experimentally validate the computational findings.

Keywords: Cystic fibrosis; Drug repositioning; Molecular docking; Molecular dynamics; Surface plasmon resonance.

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Datasets as Topic
  • Dose-Response Relationship, Drug
  • Drug Repositioning
  • Humans
  • Molecular Structure
  • Phenylalanine / antagonists & inhibitors*
  • Phenylalanine / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship


  • CFTR protein, human
  • Small Molecule Libraries
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Phenylalanine