Quinolinones as a Novel Therapeutic Strategy in ALS
Abstract
This project investigates quinolinone analogues as a novel therapeutic strategy for ALS. We previously demonstrated that these compounds display broad efficacy in cellular and zebrafish models. This study aims (i) to identify the primary biological target, (ii) optimize formulation and delivery, and (iii) investigate efficacy and best modes of delivery of the lead molecule, ML4-10. In the first year of the project, we completed the Safety Screen analysis of ML4-10. We identified the GABAA receptor as a possible primary target and identified 3-4 possible off-target hit proteins. Using proteomics, we identified 16interacting partners of ML4-10, nine of which were localized in the nucleus, and these are currently being prioritized. We also synthesized and tested new ML4-10 analogues in disease models, including salt/prodrug forms to optimize formulation/delivery. However, ML4-10remains the most active compound to date although additional analogues are being examined.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1213968
Entities
People
- Belinda Abbott
- Julie D Atkin
- Sonam Parakh
Organizations
- Macquarie University