MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational small molecule molecular glue degrader (MGD) that targets the translation termination factor GSPT1 (also known as eRF3a). It works by inducing the interaction between the E3 ubiquitin ligase component cereblon and GSPT1, leading to targeted degradation of GSPT1 protein. This mechanism disrupts protein synthesis machinery in cancer cells, particularly those with high MYC expression, exploiting their dependency on elevated levels of protein translation for uncontrolled proliferation. Preclinical studies have shown anti-tumor activity in MYC-driven tumors such as non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), neuroendocrine tumors of the prostate and bladder, androgen receptor-positive prostate cancer, and estrogen receptor-positive breast cancer. The drug is being developed by Monte Rosa Therapeutics and is currently undergoing Phase 1/2 clinical trials.