GLL398

GLL398 is an orally bioavailable, nonsteroidal selective estrogen receptor degrader (SERD) and antagonist. Developed as a boron-modified analog of GW5638 (specifically a derivative of its active metabolite GW7604), GLL398 incorporates a boronic acid functional group in place of the phenolic hydroxyl group. This modification prevents rapid phase II metabolism (glucuronidation and sulfation), significantly improving oral bioavailability while maintaining high binding affinity and degrading efficacy toward both wild-type and mutant (Y537S) estrogen receptor alpha (ERα). In preclinical models, GLL398 has demonstrated potent tumor growth inhibition and regression in MCF-7 breast cancer xenografts and patient-derived xenografts (PDX) harboring ESR1 mutations, making it a promising candidate for the treatment of endocrine-resistant breast cancer.

Other names

3-(4-(1-(4-boronophenyl)-2-phenylbut-1-en-1-yl)phenyl)acrylic acidboron-modified GW7604