MZeDT3

MZeDT3 is a first-in-class, highly selective Proteolysis Targeting Chimera (PROTAC) designed to induce the degradation of ZAKα (MAP3K20), a key kinase involved in the ribotoxic stress response (RSR). ZAKα acts as a sensor for stalled ribosomes, triggering downstream signaling pathways like p38 and JNK MAP kinases in response to various stressors, including UV radiation and ribotoxic toxins. MZeDT3 consists of a ZAKα-binding ligand (based on the scaffold of the kinase inhibitor MZe786) linked to a von Hippel-Lindau (VHL) E3 ligase recruiter. By depleting ZAKα protein levels, MZeDT3 effectively blocks the RSR, providing a powerful tool for studying the biological roles of ZAKα and potentially serving as a lead compound for treating diseases driven by aberrant RSR signaling, such as UV-induced skin damage or metabolic stress.

Other names

ZAKα PROTAC