ArticleJournal of medicinal chemistry2012
Structure-activity relationships of cyanoquinolines with corrector-potentiator activity in ΔF508 cystic fibrosis transmembrane conductance regulator protein.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Overview of CFTR activators and their recent studies for dry eye disease: a review.RSC medicinal chemistry · 2023Review
- New Insights into the Binding Features of F508del CFTR Potentiators: A Molecular Docking, Pharmacophore Mapping and QSAR Analysis Approach.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors.International journal of molecular sciences · 2020Article
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- Molecular basis of cystic fibrosis: from bench to bedside.Annals of translational medicine · 2018Review
- Partial rescue of F508del-cystic fibrosis transmembrane conductance regulator channel gating with modest improvement of protein processing, but not stability, by a dual-acting small molecule.British journal of pharmacology · 2018Article
- Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines.PloS one · 2016Article
- Rescuing ΔF508 CFTR with trimethylangelicin, a dual-acting corrector and potentiator.American journal of physiology. Lung cellular and molecular physiology · 2014Review
- Davis-Beirut reaction: route to thiazolo-, thiazino-, and thiazepino-2H-indazoles.The Journal of organic chemistry · 2014Article
- Enhancing the Potency of F508del Correction: A Multi-Layer Combinational Approach to Drug Discovery for Cystic Fibrosis.Journal of pharmacology & clinical toxicology · 2013Article
- Efficacy and safety of liposomal clarithromycin and its effect on Pseudomonas aeruginosa virulence factors.Antimicrobial agents and chemotherapy · 2013Article
- Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Functional Rescue of F508del-CFTR Using Small Molecule Correctors.Frontiers in pharmacology · 2012Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The most common CF-causing mutation, ΔF508-CFTR, produces CFTR loss-of-function by impairing its cellular targeting to the plasma membrane and its chloride channel gating. We recently identified cyanoquinolines with both corrector ("Co", normalizing ΔF508-CFTR targeting) and potentiator ("Po", normalizing ΔF508-CFTR channel gating) activities. Here, we synthesized and characterized 24 targeted cyanoquinoline analogues to elucidate the conformational requirements for corrector and potentiator activities. Compounds with potentiator-only, corrector-only, and dual potentiator-corrector activities were found. Molecular modeling studies (conformational search ⇒ force-field lowest energy assessment ⇒ geometry optimization) suggest that (1) a flexible tether and (2) a relatively short bridge between the cyanoquinoline and arylamide moieties are important cyanoquinoline-based CoPo features. Further, these CoPo's may adopt two distinct π-stacking conformations to elicit corrector and potentiator activities.
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Registered trials
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