GSPT1 MGD MRT-2359

An orally bioavailable selective molecular glue degrader (MGD) of the translational termination factor GSPT1, with potential antineoplastic activity. Upon oral administration, MRT-2359 targets and binds to GSPT1, thereby promoting complex formation between the E3 ubiquitin ligase component cereblon (CRBN) and GSPT1, and inducing GSPT1 degradation in a CRBN- and degron-dependent manner. This downregulates L-MYC and N-MYC, thereby disrupting MYC-driven protein translation and reducing MYC-oncogenic signaling. This inhibits proliferation in MYC-driven tumors. The translation termination factor GSPT1, a G-loop degron-containing protein, plays a key role in protein translation in MYC-driven cancers.