GDC-0927

GDC-0927 is a novel, potent, non-steroidal, orally bioavailable small molecule that acts as a selective estrogen receptor degrader (SERD) and antagonist. It was developed for the treatment of estrogen receptor-positive (ER+) breast cancer. Mechanistically, it binds to the estrogen receptor alpha (ERα), antagonizes its activity, and promotes its degradation. Preclinical studies demonstrated tumor regression in ER+ breast cancer models. In phase I clinical trials in postmenopausal women with advanced or metastatic ER+/HER2− breast cancer—including those with ESR1 mutations—GDC-0927 showed evidence of target engagement and pharmacodynamic activity but did not achieve objective responses; some patients achieved stable disease or clinical benefit. The drug was generally well tolerated with manageable side effects such as nausea and fatigue. Despite promising pharmacological properties and evidence of ER pathway suppression at both transcript and protein levels (>90% reduction in FES uptake; ~40% reduction in ER expression), further development was discontinued due to strategic reasons including high pill burden[1][4][6][8].

Other names

GDC-0927 RacemateGDC0927 RacemateGDC 0927 RacemateSRN-927 RacemateSRN927 RacemateSRN 927 Racemate