选择性雌激素受体下调剂的作用机制及研究进展

urrently, efforts have been made to develop new antiestrogens that display potent antiestrogenic activity, particularly toward the tamoxifen resistance breast cancer cells, selective estrogen receptor downregulator (SERDs), are kind of the compound lacks estrogen agonistic activity and leads to a rapid decrease in ER levels, especially ERα. Because such compounds have no agonistic activity but instead destabilize the ER, resulting in complete disruption of ER-mediated growth stimulation, they are pure antagonists and appear to be an effective approach to avoiding the development of antiestrogen resistance by completely blocking the activity of E2 through the inhibition of both AF1 and AF2 function. These pure antagonists have distinct action of mechanism from the conventional drugs, like tamoxifen and other SERMs. This type of ER ligand plays an important role as a second-line therapy against advanced breast cancer in patients who develop resistance to tamoxifen treatment. This review presents the recent progress in the study on the design, structure and biological activity of the synthesized SERDs for estrogen receptor.