Elacestrant

DB06374ApprovedInvestigationalSmall moleculeEstrogen Receptor Antagonists

Elacestrant is an estrogen receptor antagonist used to treat ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. It received a similar approval in the EU in September 2023.

Mechanism: Elacestrant is an oral selective estrogen receptor degrader (SERD) that binds to estrogen receptor-alpha (ERα). Breast tumors that express ERα depend on estrogen-mediated growth signaling; therefore, endocrine therapies that target the estrogen receptor (ER) are commonly used in the treatment of this type of cancer. SERDs are a type of endocrine therapy that antagonizes the transcriptional activity of the ER and promotes its degradation.
In ER-positive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibits 17β-estradiol-mediated cell proliferation and induces ERα degradation through the proteasomal pathway. Elacestrant also slows ER nuclear translocation and promotes ER turnover, disrupting downstream signaling. Elacestrant has in vitro and in vivo anti-tumor activity in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors, as well as cancer models with estrogen receptor 1 gene (ESR1) mutations.
Curator reviewed · 9 references
Primary indication: Elacestrant is indicated for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.Curator reviewed · 8 structured indications
Formula / weight: C₃₀H₃₈N₂O₂ · 458.646 g/mol (avg)
First approval: United States, 2023 · European Union, 2023
Code names: ER-306323 · RAD-1901
Brand names: Orserdu