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Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives
[Image: see text] In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014417/ https://www.ncbi.nlm.nih.gov/pubmed/35377645 http://dx.doi.org/10.1021/acs.jmedchem.1c01897 |
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author | Brusa, Irene Sondo, Elvira Falchi, Federico Pedemonte, Nicoletta Roberti, Marinella Cavalli, Andrea |
author_facet | Brusa, Irene Sondo, Elvira Falchi, Federico Pedemonte, Nicoletta Roberti, Marinella Cavalli, Andrea |
author_sort | Brusa, Irene |
collection | PubMed |
description | [Image: see text] In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules. However, their clinical use remains limited, as they fail to fully restore F508del-CFTR biological function. Indeed, the search for CFTR correctors with different and additive mechanisms has recently increased. Among them, drugs that modulate the CFTR proteostasis environment are particularly attractive to enhance therapy effectiveness further. This Perspective focuses on reviewing the recent progress in discovering CFTR proteostasis regulators, mainly describing the design, chemical structure, and structure–activity relationships. The opportunities, challenges, and future directions in this emerging and promising field of research are discussed, as well. |
format | Online Article Text |
id | pubmed-9014417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-90144172022-04-19 Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives Brusa, Irene Sondo, Elvira Falchi, Federico Pedemonte, Nicoletta Roberti, Marinella Cavalli, Andrea J Med Chem [Image: see text] In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules. However, their clinical use remains limited, as they fail to fully restore F508del-CFTR biological function. Indeed, the search for CFTR correctors with different and additive mechanisms has recently increased. Among them, drugs that modulate the CFTR proteostasis environment are particularly attractive to enhance therapy effectiveness further. This Perspective focuses on reviewing the recent progress in discovering CFTR proteostasis regulators, mainly describing the design, chemical structure, and structure–activity relationships. The opportunities, challenges, and future directions in this emerging and promising field of research are discussed, as well. American Chemical Society 2022-04-04 2022-04-14 /pmc/articles/PMC9014417/ /pubmed/35377645 http://dx.doi.org/10.1021/acs.jmedchem.1c01897 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brusa, Irene Sondo, Elvira Falchi, Federico Pedemonte, Nicoletta Roberti, Marinella Cavalli, Andrea Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives |
title | Proteostasis Regulators
in Cystic Fibrosis: Current
Development and Future Perspectives |
title_full | Proteostasis Regulators
in Cystic Fibrosis: Current
Development and Future Perspectives |
title_fullStr | Proteostasis Regulators
in Cystic Fibrosis: Current
Development and Future Perspectives |
title_full_unstemmed | Proteostasis Regulators
in Cystic Fibrosis: Current
Development and Future Perspectives |
title_short | Proteostasis Regulators
in Cystic Fibrosis: Current
Development and Future Perspectives |
title_sort | proteostasis regulators
in cystic fibrosis: current
development and future perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014417/ https://www.ncbi.nlm.nih.gov/pubmed/35377645 http://dx.doi.org/10.1021/acs.jmedchem.1c01897 |
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