This project aims to develop a new class of modulators also active on rare CFTR mutations. The research group plans to synthesize and test the compounds following an iterative process of chemical synthesis and in-vitro functional evaluations to select and to optimize a small number of compounds. The project is based on the complementarity of the laboratories of Prof. Barraja and Dr. Galietta.

The research groups share their expertise in synthetic organic chemistry and pharmacology and they use consolidated procedures of chemical synthesis.

Thanks to previous funded projects by FFC Ricerca, FFC#4/2018 and FFC#3/2020, researchers have identified a molecule, belonging to a new class of correctors. After the optimizations of this first obtained molecule, a new one, called PP028, was also generated. This molecule, was already tested on primary cells obtained from CF patients, showing a strong activity, especially when combined with known correctors.

The “Molecole 3.0” project aims to further improve the properties of this new class of correctors, through the coordinated work of pharmaceutical chemists who will generate new derivatives and by biologists who will evaluate the effectiveness of the compounds with in-vitro assays.

The synthesis process and the functional evaluations will allow to improve the potency and efficacy of the selected compounds. The functional tests will be conducted with in vitro tests, also using the Primary Culture Service (Servizio Colture Primarie) by FFC Ricerca. The optimization of the molecules will also take into account the properties of solubility, metabolic stability and the absence of toxicity, which are essential for any drug development. The ultimate goal of the project is to select a compound that can be considered for preclinical and clinical development.

Check the Phase 2 of the project.