PGD97 is a selective cyclic peptide inhibitor targeting the CAL/CFTR interaction, with its desulfurization-cyclized form exhibiting a KD value of 6 nM for the CAL PDZ domain. It shows a selectivity of at least 130-fold over the NHERF1/2 PDZ domains. PGD97 stabilizes F508del-CFTR on the cell membrane, enhancing CFTR function necessary for normal pulmonary fluid balance. This compound is applicable in cystic fibrosis research.

PGD97 (Compound 24c) demonstrates strong cellular entry efficiency in HeLa cells, relative to CPP9 at 61. It remains highly stable in human serum over 24 hours at 37 °C, with approximately 77% of the peptide intact. In HCT116 cells, PGD97 (5 μM) penetrates the cell membrane effectively, rapidly reduces to its bioactive linear form (24) through intracellular thiols, and undergoes partial degradation within the membrane. The compound exhibits no significant cytotoxicity in cell lines CFBE41o-, HCT116, and H358 at concentrations of 0-50 μM over 72 hours. PGD97 (100 nM) increases the short-circuit current in patient-derived F508del gene-homologous cells by approximately threefold and enhances the efficacy of small-molecule correctors, like VX-661, by approximately twofold (with an EC50 of about 10 nM).