Publications by authors named "Felix Nawa"
J Med Chem
September 2024
Article Synopsis
- The activation of nuclear retinoid X receptors (RXRs) involves releasing corepressors and recruiting coactivators, influencing gene activation or repression.
- Research identified a synthetic agonist that significantly increases the binding of PGC1α (a coactivator) to RXR, unlike the natural ligand 9-cis retinoic acid.
- The study produced three related RXR agonists with varying abilities to enhance PGC1α recruitment, suggesting potential new therapies through targeted RXR-PGC1α interactions via selective coregulator modulation.
Article Synopsis
- Nurr1 (NR4A2) is a crucial transcription factor in the central nervous system that plays protective and anti-inflammatory roles, making it a target in treating neurodegenerative diseases like Parkinson's and Alzheimer's.
- Current research has focused on developing Nurr1 agonists, but there is a gap in creating inverse agonists that inhibit its activity.
- This study details the structure-activity relationship of oxaprozin, identifying its potential as a moderate inverse Nurr1 agonist and RXR agonist, paving the way for future development of more selective and effective Nurr1 inverse agonists.
Article Synopsis
- Retinoid X receptors (RXRs) are important proteins that help regulate various biological processes like cell differentiation and death, but existing RXR agonists lack specificity and effectiveness.
- Researchers are working to develop better RXR modulators by combining structures from natural ligands, like those derived from vitamin A and valerenic acid, to enhance their binding properties and effectiveness.
- They successfully created a new, more potent RXR agonist by modifying an oxaprozin-derived compound and replacing problematic elements to avoid interference in biological assays, leading to a highly optimized new chemical probe for RXR.
Article Synopsis
- Generative neural networks, specifically chemical language models (CLMs) trained on SMILES, can create new bioactive molecules, particularly useful for drug discovery.
- Traditional CLMs require many template molecules, making it hard to work with orphan targets that have limited known ligands.
- By fine-tuning a CLM with a single Nurr1 agonist and employing a novel design approach, researchers developed new Nurr1 agonists that show impressive potency and structural novelty, demonstrating the effectiveness of CLMs in low-data situations.
