ArticleCell2024
Structure-based discovery of CFTR potentiators and inhibitors.
Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- A Non-Channel Function of CFTR: Attenuating Mitochondrial Oxidative Stress and Cardiomyocyte Senescence via Stabilization by USP45.Aging cell · 2026Article
- Remodeling the pathological airway: advanced nanotechnology for diagnostics and therapeutics in cystic fibrosis.Journal of nanobiotechnology · 2026Review
- Targeting the Protein-Membrane Interface Enables Design of Long-Acting CFTR Potentiators.ACS chemical biology · 2026Article
- Distinct CFTR Mutation Spectrum and Atypical Clinical Presentations in Chinese Patients with Cystic Fibrosis.International journal of molecular sciences · 2026Review
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Structure-guided design of picomolar-level macrocyclic TRPC5 channel inhibitors with antidepressant activity.Acta pharmaceutica Sinica. B · 2026Article
- Batched Bayesian Optimization by Maximizing the Probability of Including the Optimum.Journal of chemical information and modeling · 2025Article
- Article
- Esc peptides and derivatives potentiate the activity of CFTR with gating defects and display antipseudomonal activity in cystic fibrosis-like lung disease.Cellular and molecular life sciences : CMLS · 2025Article
- Virtual library docking for cannabinoid-1 receptor agonists with reduced side effects.Nature communications · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- CFTR as a therapeutic target for severe lung infection.American journal of physiology. Lung cellular and molecular physiology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, whereas its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed. Here, we combine molecular docking, electrophysiology, cryo-EM, and medicinal chemistry to identify CFTR modulators. We docked ∼155 million molecules into the potentiator site on CFTR, synthesized 53 test ligands, and used structure-based optimization to identify candidate modulators. This approach uncovered mid-nanomolar potentiators, as well as inhibitors, that bind to the same allosteric site. These molecules represent potential leads for the development of more effective drugs for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel drug discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.