Small molecule modulators of cystic fibrosis transmembrane conductance regulator (CFTR): Structure, classification, and mechanisms.

The advent of small molecule modulators targeting the cystic fibrosis transmembrane conductance regulator (CFTR) has revolutionized the treatment of persons with cystic fibrosis (CF) (pwCF). Presently, these small molecule CFTR modulators have gained approval for usage in approximately 90 % of adult pwCF. Ongoing drug development endeavors are focused on optimizing the therapeutic benefits while mitigating potential adverse effects associated with this treatment approach. Based on their mode of interaction with CFTR, these drugs can be classified into two distinct categories: specific CFTR modulators and non-specific CFTR modulators. Specific CFTR modulators encompass potentiators and correctors, whereas non-specific CFTR modulators encompass activators, proteostasis modulators, stabilizers, reader-through agents, and amplifiers. Currently, four small molecule modulators, all classified as potentiators and correctors, have obtained marketing approval. Furthermore, numerous novel small molecule modulators, exhibiting diverse mechanisms of action, are currently undergoing development. This review aims to explore the classification, mechanisms of action, molecular structures, developmental processes, and interrelationships among small molecule CFTR modulators. The current review is kept forth to compile a summary of the structure, classification, and mechanism of small molecule modulators of CFTR. [Display omitted] • Small molecule modulators targeting the cystic fibrosis transmembrane conductance regulator (CFTR) have significantly improved cystic fibrosis (CF) treatment. • Various mechanisms categorize those modulators. • Modulators within the same class share Structural similarities. • Medicinal chemistry optimization of modulators reveals potential structure-activity relationships. [ABSTRACT FROM AUTHOR]