Many CFTR mutants do not fully respond to the already available therapies and there is an urgent need for new drugs able to restore the CFTR functionality in those people with cystic fibrosis (CF) carrying (ultra)rare mutations.
Increasing the number of available drugs active on different CFTR mutations can lay the basis for personalized medicine. Understanding the mechanism of correction/potentiation of CFTR can boost the development of new drugs.
Thanks to previous studies (FFC#3/2021), the researchers identified a novel potentiator of CFTR. In this project, researchers will synthesize and test a series of compounds derived from the previous one. Compounds will be tested on cells derived from patients, then the most promising ones will be also tested on mice (in collaboration with FFC Ricerca CFaCore) to evaluate if the compounds can be effectively administered as oral drugs and may exert the desired effect. The project will include structural studies to describe the effect of the drugs on the protein physiology and computational studies to visualize and predict the protein behavior upon interacting with the compounds.
The final aim of the research is to furnish novel drug candidates that will be in future tested in patients with different (ultra)rare mutations in combination with known drugs to evaluate their clinical potential. Compounds active on a specific mutation will be further developed to increase the arsenal of drugs.