ASK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that is responsible for mediating the cellular stress response. In neurological disease, activation of this pathway has been linked to the pathogenesis of several diseases including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) or stroke. To test the therapeutic value of inhibiting ASK1 in the central nervous system (CNS) we have identified potent, selective and brain penetrant ASK1 inhibitors that had suitable profile for chronic administration. A summary of the medicinal chemistry effort leading to these novel inhibitors, followed by proof of pharmacology studies in animal models of neurological disease will be discussed.

Discovery of apoptosis signal-regulating kinase 1 (ASK1) inhibitors that modulate brain inflammation

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.