Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases. In this presentation, we will highlight our approach to balancing the property space of kinase inhibitors for the CNS. Starting from a high-throughput screening hit, we used structure-based drug design combined with a focus on CNS drug-like properties to identify GDC-0134, which advanced to clinical evaluation as a potential treatment of amyotrophic lateral sclerosis (ALS).

Discovery of GDC-0134: A potent, selective, and brain-penetrant dual leucine zipper kinase Inhibitor

ACS Spring Meeting 2021

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