A selective estrogen receptor degrader or downregulator (SERD) is a type of drug that selectively binds to the estrogen receptor (ER) and induces its degradation, and thus causes its downregulation. SERDs are used in the treatment of estrogen receptor-positive breast cancer, particularly in cases where tumors have developed resistance to other forms of endocrine therapy, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors.
The mechanism of action of SERDs involves binding to the estrogen receptor, leading to a conformational change that facilitates recruitment of cellular machinery to degrade the receptor protein. By promoting degradation of the estrogen receptor, SERDs effectively inhibit estrogen signaling within cancer cells, thereby suppressing tumor growth.
A common SERD used in clinical practice is fulvestrant. Fulvestrant is administered as an intramuscular injection and is indicated for the treatment of advanced breast cancer in postmenopausal women whose cancer has progressed following anti-estrogen therapy.
As of 2026 the marketed SERDs are fulvestrant (brand name Faslodex),, elacestrant (brand name Orserdu), imlunestrant (Inluriyo), and vepdegestrant (Veppanu). The clinical success of fulvestrant led to efforts to discover and develop a parallel drug class of selective androgen receptor degraders (SARDs).
Investigational
Fulvestrant requires intramuscular injections once every two weeks. In response, pharmaceutical companies are currently developing oral SERDs. Among products in development are:
Monofunction (ER ligand) hydrophobic tag degradation: + List of Selective Estrogen Receptor Degraders (SERDs) Modality INN Research Code Sponsor Comment Amcenestrant SAR 439859 Sanofi Brilanestrant Genentech Camizestrant AZD9833 AstraZeneca Elacestrant Radius Giredestrant Roche Imlunestrant LY3484356 Eli Lilly Palazestrant OP-1250 Olema Pharmaceuticals H3B-6545 Eisai Co Ltd SERCA ZB716 EnhancedBio/Zenopharm Fulvestrant boronic acid Bexirestrant Menarini Etacstil GW-5638 Bristol Myers-Squibb combined SERM and SERD Rintodestrant G1T48 G1 Therapeutics Taragarestrant D-0502 Inventisbio LSZ102 Novartis ZN-c5 Zentalis SHR9549 Jiangsu Hengrui Vepdegestrant ARV-471 Arvinas AC 699 Accutar Biotechnology
The oral SERDs target ER-positive/HER2-negative breast cancer and are tested as monotherapy and in combination with other drugs such as the CDK inhibitor palbociclib (Ibrance). AZD 9496 GDC 0927 H3B 5942 GLL 398
See also Aromatase inhibitor Estrogen deprivation therapy
References