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Targeting the Underlying Defect in CFTR with Small Molecule Compounds

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Cystic Fibrosis

Part of the book series: Respiratory Medicine ((RM))

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Abstract

Cystic fibrosis (CF), or mucoviscidosis, is an autosomal recessive disease that presents when a patient has two variant alleles of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein. Currently, 2031 genetic variants have been identified in CFTR, of which 312 are known to be disease causing. Variants for which the functional effects on CFTR are known have been sorted into six general molecular classes based on their underlying cell biology (Fig. 24.1). It is important to note that although the class system is a useful construct, the properties of individual mutations often overlap significantly, with many variants having features of multiple classes. For example, the most common variant in the United States, F508del, found in over 70% of patients, has features of Class II (altered protein maturation) and Class III (altered channel function).

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Pulmonary and Sleep Medicine, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    Jennifer S. Guimbellot

  2. Department of Medicine, Department of Pediatrics, Department of Cell Developmental and Integrative Biology, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    Steven M. Rowe

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  1. Jennifer S. Guimbellot
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  2. Steven M. Rowe
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Correspondence to Steven M. Rowe .

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Editors and Affiliations

  1. The University of North Carolina at Chapel Hill, Department of Pediatrics, UNC Children’s Hospital, Chapel Hill, NC, USA

    Stephanie Duggins Davis

  2. Department of Pediatrics, University of Washington School of Medicine, Division of Pulmonary and Sleep Medicine, Seattle Children’s Hospital, Seattle, WA, USA

    Margaret Rosenfeld

  3. Department of Pediatrics, Indiana University School of Medicine, Division of Pediatric Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children at IU Health, Indianapolis, IN, USA

    James Chmiel

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Guimbellot, J.S., Rowe, S.M. (2020). Targeting the Underlying Defect in CFTR with Small Molecule Compounds. In: Davis, S., Rosenfeld, M., Chmiel, J. (eds) Cystic Fibrosis. Respiratory Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-42382-7_24

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