About 200 compounds were synthesized and analysed, obtaining useful information on the relationships between chemical structure and biological activity of these correctors using biochemical tests and in-vitro evaluations. The PP028 compound was selected for further mechanistic studies as the researchers speculate that it represents a new family of pharmacological agents acting on a second site of the CFTR protein. The researchers report that PP028, probably of class 3, shows a high metabolic stability but a low kinetic solubility that needs to be improved. The results of the PP028 activity in combination with other correctors are also reported, showing a synergistic effect with class 2 but not with class 3.

Pubblications

• Carbone A, Montalbano A, Musante I et al. Furocoumarins as multi-target agents in the treatment of cystic fibrosis, European Journal of Medicinal Chemistry (2019), 180, 283
• Spanò V, Barreca M, Cilibrasi V, Genovese M, Renda M, Montalbano A, Galietta LJV, Barraja P. Evaluation of Fused Pyrrolothiazole Systems as Correctors of Mutant CFTR Protein. Molecules. 2021 Feb 26;26(5):1275. doi: 10.3390/molecules26051275. PMID: 33652850; PMCID: PMC7956813.

Congress abstracts

• Scudieri P, Musante I, Spanò V et al. Determination of drug sensitivity of orphan CFTR mutations: no patient left behind, North American Cystic Fibrosis Conference (NACFC), October 31 – November 2, 2019 Nashville, TN (USA)
• Spanò V, Montalbano A, Musante I et al. Discovery of new second site correctors of Cystic Fibrosis transmembrane conductance regulator (CFTR), XXVI National Meeting in Medicinal Chemistry, Milan, Ca’ Granda, July 16-19, 2019