EC Pulmonology and Respiratory Medicine

Cystic fibrosis (CF) is a life-threatening genetic disorder affecting approximately 70,000 people worldwide, caused by mutations in the CFTR gene that lead to defective chloride ion transport across epithelial membranes. This literature review examines the molecular chemistry underlying CF pathophysiology and the development of targeted therapeutics that address the root causes of the disease. Recent advances in structural biology have revealed the detailed architecture of the CFTR protein, enabling the rational design of small-molecule modulators like ivacaftor, lumacaftor, and elexacaftor that directly target protein defects. These CFTR modulators represent a paradigm shift from symptom management to precision medicine approaches that restore protein function. Emerging therapeutic strategies include read-through agents for nonsense mutations, proteostasis modulators, and novel targets like the epithelial sodium channel. Gene therapy approaches continue to show promise despite delivery challenges. The molecular understanding of CFTR structure-function relationships has transformed CF treatment, with combination therapies now providing substantial clinical benefits for many patients. This review synthesizes current knowledge of the chemical mechanisms underlying CF therapeutics and identifies future directions for drug development.

 Keywords: Cystic Fibrosis (CF); CFTR Gene; Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

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