Palazestrant — Investigational Agent
Selective Estrogen Receptor Degrader · Phase 3 · Olema Oncology
Mechanism of Action
Oral complete estrogen receptor antagonist and degrader (CERAN/SERD). Palazestrant binds the estrogen receptor (ER) and both blocks and degrades it, functioning as a complete antagonist that inactivates both activation function domains (AF-1 and AF-2) of the receptor. This distinguishes it from earlier selective ER modulators (SERMs like tamoxifen) and first-generation SERDs (fulvestrant), which incompletely suppress ER transcriptional activity. By fully shutting down ER-driven transcription and promoting receptor degradation, palazestrant suppresses proliferation of ER-dependent breast…
Investigational Indications
- ER+/HER2- advanced or metastatic breast cancer (following endocrine and CDK4/6 inhibitor therapy)
- ESR1-mutant ER+ breast cancer
- ER+ breast cancer in combination with CDK4/6 inhibitors