A5020582292- Cystic Fibrosis Research Advances
- Advanced biosensing and bioanalysis techniques
- Asthma and respiratory diseases
- Legume Nitrogen Fixing Symbiosis
- Nematode management and characterization studies
- Inhalation and Respiratory Drug Delivery
- Computational Drug Discovery Methods
- Biomedical and Engineering Education
- Pharmaceutical studies and practices
- Intravenous Infusion Technology and Safety
- Immunodeficiency and Autoimmune Disorders
- ECG Monitoring and Analysis
- Chemistry and Chemical Engineering
- Flow Measurement and Analysis
- Protein purification and stability
- Advanced Malware Detection Techniques
- Neonatal Respiratory Health Research
University of Lisbon
2021-2025
The deletion of a phenylalanine at position 508 (p.Phe508del) in the CFTR anion channel is most prevalent variant people with Cystic Fibrosis (CF). This impairs folding and stability CF transmembrane conductance regulator (CFTR) protein, resulting its defective trafficking premature degradation. Over last years, therapeutic accomplishments have been attained developing small molecules that partially correct p.Phe508del-CFTR defects; however, mechanism action (MoA) these compounds has only...
The monogenic rare disease Cystic Fibrosis (CF) is caused by mutations in the gene encoding CF transmembrane conductance (CFTR) protein, an anion channel expressed at apical plasma membrane of epithelial cells. discovery and subsequent development CFTR modulators—small molecules acting on basic molecular defect CF—have revolutionized standard care for people with (PwCF), thus drastically improving their clinical features, prognosis, quality life. Currently, four these drugs are approved use:...
Background: The potentiator VX-770 (ivacaftor) has been approved as a monotherapy for over 95 cystic fibrosis (CF)-causing variants associated with gating/conductance defects of the CF transmembrane conductance regulator (CFTR) channel. However, despite its therapeutic success, only partially restores CFTR activity many these variants, indicating they may benefit from combination potentiators exhibiting distinct mechanisms action (i.e., co-potentiators). We previously identified LSO-24,...
The R334W (c.1000C>T, p.Arg334Trp) is a rare cystic fibrosis (CF)-causing mutation for which no causal therapy currently approved. This leads to significant reduction of CF transmembrane conductance regulator (CFTR) channel that still allows residual function. Potentiators are small molecules interact with CFTR protein at the plasma membrane enhance CFTR-dependent chloride secretion, representing thus pharmacotherapies targeting root cause disease. Here, we generated new bronchial epithelial...
Although some therapeutic progress has been achieved in developing small molecules that correct F508del-CFTR defects, the mechanism of action (MoA) these compounds remain poorly elucidated. Here, we investigated effects and MoA MCG1516A, a newly developed corrector. MCG1516A on wild-type (WT) were assessed by immunofluorescence microscopy, biochemical functional assays both cell lines intestinal organoids. To shed light evaluated its additivity to FDA-approved corrector VX-661, low...
The most prevalent cystic fibrosis (CF)-causing mutation - F508del impairs the folding of CFTR protein, resulting in its defective trafficking and premature degradation. Small molecules termed correctors may rescue F508del-CFTR therefore constitute promising pharmacotherapies acting on fundamental cause disease. Here, we screened a collection triazole compounds to identify novel correctors. functional primary screen identified four hit (LSO-18, LSO-24, LSO-28, LSO-39), which were further...