IACS-52825

**IACS-52825** is a potent and highly selective small molecule inhibitor of dual leucine zipper kinase (DLK, also known as MAP3K12), a neuronally enriched kinase that activates the MAPK-JNK cascade to mediate axon degeneration under stress conditions. Developed by the Institute for Applied Cancer Science (IACS) at The University of Texas MD Anderson Cancer Center in collaboration with the Neurodegenerative Consortium (NDC) and partners including Evotec and Magnolia Neurosciences, it demonstrates excellent brain penetration, pharmacokinetic properties, and efficacy in reversing mechanical allodynia in mouse models of chemotherapy-induced peripheral neuropathy (CIPN) caused by agents like cisplatin. With a Kd of 1.3 nM and IC50 of 107 nM, it was advanced to preclinical development but ultimately discontinued due to optic nerve swelling toxicity in non-human primates without an adequate therapeutic window.[1][2][4]