The introduction of biologics for the treatment of severe upper and lower (type 2) airway inflammation has been a gamechanger in the management of these diseases. Biologics are injectable medications targeting different molecules relevant in (type 2) inflammation in patients with severe (type 2) airway diseases, like asthma, eosinophilic chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS) and those who remain uncontrolled despite regular treatment (1-3). After the phase 3 trials, showing significant impact on symptoms, quality of life and interventions like surgery (for the upper airways) and exacerbations needing hospitalisation (for the lower airways), biologics are now used in daily practice in many parts of the world (4, 5). This pocket guide is aimed at all specialists treating adult patients with severe airway disease.
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http://dx.doi.org/10.4193/Rhin24.510 | DOI Listing |
RSC Chem Biol
March 2025
Novartis Biomedical Research Fabrikstrasse 2 CH-4056 Basel Switzerland
Many disease-relevant and functionally well-validated targets are difficult to drug. Their poorly defined 3D structure without deep hydrophobic pockets makes the development of ligands with low molecular weight and high affinity almost impossible. For these targets, incorporation into a ternary complex may be a viable alternative to modulate and in most cases inhibit their function.
View Article and Find Full Text PDFNat Commun
March 2025
Department of Biochemistry, Tennis Court Road, Cambridge, UK.
Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids.
View Article and Find Full Text PDFJ Med Chem
March 2025
Revolution Medicines, Inc., Redwood City, California 94063, United States.
Oncogenic RAS mutations are among the most common in human cancers. To target the active, GTP-bound state of RAS(ON) directly, we employed an innovative tri-complex inhibitor (TCI) modality. Formation of a complex with an intracellular chaperone protein CypA, an inhibitor, and a target protein RAS blocks effector binding, inhibiting downstream RAS signaling and tumor cell proliferation.
View Article and Find Full Text PDFInt J Biol Macromol
March 2025
Key Laboratory of Food Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address:
Affinity plays an essential role in the rate and stability of enzyme-catalyzed reactions, thus directly impacting the catalytic activity. In general, the predictive method for protein-ligand binding affinity mainly relies on high-resolution protein crystal structure data; however, some protein crystals are difficult to culture, time-consuming, and expensive to obtain. In this study, two sequence-based neural network deep learning models - DeepPQK and DeepQK, were constructed to predict the protein-ligand binding affinity.
View Article and Find Full Text PDFJ Phys Chem B
March 2025
Department of Chemistry & Chemical Biology, Indian Institute of Technology (ISM), Dhanbad, Dhanbad 826004, India.
Targeted therapy with an allosteric inhibitor (AIs) is an important area of research in patients with epidermal growth factor receptor (EGFR) mutations. Current treatment of nonsmall cell lung cancer patients with EGFR mutations using orthosteric inhibitors faces challenges like resistance and stopping over phosphorylation. Notably AIs have been introduced to overcome this resistance and increase inhibitory potency that binds to pockets other than the ATP-binding site (orthosteric site).
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