Current Progresses and Trends in the Development of Progesterone Receptor Modulators.
The progesterone receptor (PR) is a ligand-activated steroid receptor in the nuclear receptor (NR) superfamily of transcription factor. Besides gynecological and obstetrical indications, the involvement/mechanism of PR in many other diseases, such as oncology, neurology, immunology, etc. has been revealed and studied in recent decades. Therapeutic agents that selectively activate or inhibit PR have been developed. PR agonists have generally been used in oral contraception and postmenopausal hormone replacement therapy (HRT), typically in combination with estrogens. PR antagonists and selective PR modulators (SPRMs) can be useful therapies for hormone dependent breast and prostate cancers, nonmalignant chronic conditions such as fibroids, and endometriosis. This review provides an overview and detailed discussions about the recent development of chemical structures of the PR ligands, their structural characteristics (particularly those contributing to their activity and selectivity), in vitro/in vivo studies and clinical trial outcomes, and the synthetic methodologies.
Wenlu
W
Li
Xi
X
Li
Bin
B
Zhang
Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory, the Graduate School at Shenzhen, Tsinghua University, Shenzhen, P.R. China.
Chunmei
C
Gao
Yuzong
Y
Chen
Yuyang
Y
Jiang
D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000072471:Heterocyclic Compounds, Fused-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D020249:Hormone Replacement Therapy; D006801:Humans; D006840:Hydrocarbons, Alicyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism
D001880:Boranes; D003374:Coumarins; D000072471:Heterocyclic Compounds, Fused-Ring; D006840:Hydrocarbons, Alicyclic; D007211:Indoles; D008024:Ligands; D011980:Receptors, Progesterone; D013256:Steroids; D014807:Vitamin D; C030123:coumarin