Reactome | ESR1 binds ESR1 antagonists

ESR1 binds ESR1 antagonists

Stable Identifier

R-HSA-9716913

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Estrogen receptor alpha (ERα, NR3A1, nuclear receptor subfamily 3 group A member 1), encoded by the ESR1 gene, is a nuclear hormone receptor that is activated by the sex hormone estrogen. ESR1 can mediate the physiological development and function of various organ systems, including the reproductive, central nervous, skeletal, and cardiovascular systems (Kassem 1997). Accordingly, ESR1 is widely expressed throughout the body.

Antiestrogens (aka estrogen antagonists or estrogen blockers) are a class of drugs which prevent endogenous estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (selective estrogen receptor modulators (SERMs)) or inhibiting/suppressing estrogen production (selective estrogen receptor downregulators (SERDs)) (Kuiper et al. 1997, Sasson 1991, Fan et al. 2007). SERMs include tamoxifen (Wang et al. 2004), clomifene (Kurosawa et al. 2010), bazedoxifene (Toniti et al. 2011) and raloxifene (Schafer et al. 1999), and a SERD drug is fulvestrant (Schmidt et al. 2003).

Bazedoxifene is used in the treatment of moderate to severe vasomotor symptoms associated with menopause and for postmenopausal osteoporosis (Genant 2011, Rossini et al. 2013). Fulvestrant used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women (Lee et al. 2017, Lei et al. 2020). Clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome (Hughes et al. 2010). Raloxifene medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. It is also used to reduce the risk of breast cancer in those at high risk (Scott et al. 1999). Tamoxifen is used for the treatment of both early and advanced estrogen receptor-positive (ER-positive or ER+) breast cancer in pre- and postmenopausal women (Jordan 2021). Tamoxifen is also used for ovulation induction to treat infertility in women with anovulatory disorders.

Literature References

PubMed ID	Title	Journal	Year
10485477	The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor Tonetti, DA, Liu, H, Schafer, JI, Jordan, VC	Cancer Res	1999
11150164	Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists Katzenellenbogen, BS, Tedesco, R, Katzenellenbogen, JA, Sun, J, Carlson, K, Coletta, CJ, Nishiguchi, G, Stauffer, SR	J. Med. Chem.	2000
9048584	Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta Grandien, K, Gustafsson, JA, Nilsson, S, Enmark, E, Häggblad, J, Kuiper, GG, Carlsson, B	Endocrinology	1997
12672240	De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor Peter, MG, Feher, M, Mercure, J, Tremblay, GB, Pagé, M, Schmidt, JM, Kalbakji, A, Redden, PR, Dunn-Dufault, R	J. Med. Chem.	2003
22393957	Binding capacity of ER-α ligands and SERMs: comparison of the human, dog and cat Suthiyotha, N, Toniti, W, Jenwitheesuk, E, Puchadapirom, P	Asian Pac J Cancer Prev	2011
20379036	Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors alpha and beta Taketani, Y, Momoeda, M, Inoue, S, Kurosawa, T, Hiroi, H	Endocr J	2010
14605097	Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1 Edwards, EA, Liss, SN, Fulthorpe, R, Wang, DY	Mol Endocrinol	2004