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.
[1] 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.
[1] 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.
[2] The clinical success of fulvestrant led to efforts to discover and develop a parallel drug class of selective androgen receptor degraders (SARDs).
Among products in development are:[4] Monofunction (ER ligand) hydrophobic tag degradation: 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).