The Use of High-Quality Chemical Tools to Rescue TBK1 Function and Identify Novel ATP-Competitive Targets in ALS
Abstract
Kinases are an important class of proteins that are targeted by nearly 50 small molecule FDA-approved drugs. In light of this incredible success, it is remarkable that not a single kinase drug has been approved to treat a neurological disorder. There is a need for new targets and new approaches to treating ALS. We propose that kinases can be targeted to help ALS patients. Kinases play essential roles in many human pathways, including some that are not properly functioning in the case of ALS. The buildup of proteins in the brains of patients in ALS, for example, is proposed to be regulated by various kinases. If we can force these pathways to correctly function using kinase-targeting small molecules that could ultimately become drugs, then we can offer new treatment options to ALS patients that currently do not have efficacious drug options available to them. If our molecules were developed into drugs, then they would not address symptoms like the two currently available FDA-approved ALS drugs. Instead, these drugs would eliminate one cause of ALS and would thus alter the course of the disease, with the potential to have more long-term benefits to patients in terms of prolonged survival. The broad applicability of our strategy would impact nearly all ALS patients, since protein buildup is common to nearly all people with the disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010117
Entities
People
- Alison D Axtman
Organizations
- United States Army
- University of North Carolina at Chapel Hill