GLR203801

GLR203801 is an orally bioavailable estrogen receptor (ER) proteolysis-targeting chimera (PROTAC) degrader developed by Gan & Lee for the treatment of estrogen receptor-positive (ER+) breast cancer. Utilizing a novel cereblon (CRBN) ligand, GLR203801 recruits the E3 ubiquitin ligase complex to induce the ubiquitination and subsequent proteasomal degradation of both wild-type and mutant (Y537S and D538G) estrogen receptor alpha (ERα). In preclinical studies, GLR203801 demonstrated robust ER degradation, profound inhibition of ER-regulated genes (such as GREB1 and PR), and superior antitumor efficacy compared to ARV-471 in multiple ER+ xenograft models. It also showed synergistic antitumor activity when combined with CDK4/6 inhibitors.