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RESEARCH PRODUCT
An overview on chemical structures as ΔF508-CFTR correctors
Anna CarboneVirginia SpanòAlessandra MontalbanoPaola BarrajaLuis J. V. GaliettaPaolo Scudierisubject
Protein FoldingCystic FibrosisCFTR correctorMutantCystic Fibrosis Transmembrane Conductance RegulatorPyrimidinonesmedicine.disease_cause01 natural sciencesF508del-CFTR03 medical and health sciencesMutant proteinDrug DiscoverymedicineAnimalsHumansCFTR030304 developmental biologyPharmacology0303 health sciencesMutationCFTR correctorsbiology010405 organic chemistryChemistryOrganic ChemistryCFTR; CFTR correctors; Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; F508del-CFTR; Animals; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Mutation; Protein Folding; Pyrimidinones; ThiazolesGeneral MedicineSettore CHIM/08 - Chimica FarmaceuticaSmall moleculeCystic fibrosis transmembrane conductance regulator0104 chemical sciencesCell biologyThiazolesMechanism of actionCystic fibrosiMutationbiology.proteinmedicine.symptomProtein Aδf508 cftrdescription
Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key chemical structures and modifications that are required for mutant protein rescue.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-01-01 | European Journal of Medicinal Chemistry |