Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors

Dual leucine zipper kinase (DLK) and leucine zipper-bearing kinase (LZK) have emerged as key regulators of neuronal degeneration and axon growth.  WuXi AppTec scientists recently contributed to a research article in the Journal of Medicinal Chemistry demonstrating the use of ligand- and structure-based drug design approaches to discover an amino-pyrazine chemical series of DLK and LZK inhibitors.  Optimization efforts uncovered a potent and selective molecule which exhibited favorable modulation of biomarkers in a SOD1 mouse model of amyotrophic lateral sclerosis.

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