WAY-200070
WAY-200070 is a synthetic, nonsteroidal, highly selective agonist of ERβ.[1][2] It possesses 68-fold selectivity for ERβ over ERα (EC50 = 2 nM and 155 nM, respectively).[1] WAY-200070 has been found to enhance serotonergic and dopaminergic neurotransmission in the central nervous system, and produces antidepressant- and anxiolytic-like effects in animals.[2] It has been proposed as a potential novel antidepressant/anxiolytic agent.[2] WAY-200070 has also been found to produce antidiabetic effects in animals,[3] and may also be beneficial for the treatment of certain inflammatory conditions.[1]
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| Formula | C13H8BrNO3 |
| Molar mass | 306.115 g·mol−1 |
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Due to its selectivity for ERβ, WAY-200070 is inactive in various assays of classic estrogen action, such as uterotrophic and osteopenia.[1] Moreover, WAY-200070 does not affect luteinizing hormone or follicle-stimulating hormone or inhibit ovulation, indicating that it does not suppress the hypothalamic-pituitary-gonadal axis, and as ERα and not ERβ is implicated in breast development, would not be expected to cause growth of the breasts at doses that are selective for activation of ERβ.[4] In fact, ERβ activation may actually suppress breast growth,[4] and in accordance with this, WAY-200070 was shown to augment the efficacy of tamoxifen in in vitro models of breast cancer.[5] As such, WAY-200070 and other selective ERβ agonists might prove to be safe and tolerable for medical use in both premenopausal and postmenopausal women and in individuals of either sex.
References
- Malamas MS, Manas ES, McDevitt RE, Gunawan I, Xu ZB, Collini MD, Miller CP, Dinh T, Henderson RA, Keith JC, Harris HA (2004). "Design and synthesis of aryl diphenolic azoles as potent and selective estrogen receptor-beta ligands". J. Med. Chem. 47 (21): 5021–40. doi:10.1021/jm049719y. PMID 15456246.
- Hughes ZA, Liu F, Platt BJ, Dwyer JM, Pulicicchio CM, Zhang G, Schechter LE, Rosenzweig-Lipson S, Day M (2008). "WAY-200070, a selective agonist of estrogen receptor beta as a potential novel anxiolytic/antidepressant agent". Neuropharmacology. 54 (7): 1136–42. doi:10.1016/j.neuropharm.2008.03.004. PMID 18423777.
- Alonso-Magdalena P, Ropero AB, García-Arévalo M, Soriano S, Quesada I, Muhammed SJ, Salehi A, Gustafsson JA, Nadal A (2013). "Antidiabetic actions of an estrogen receptor β selective agonist" (PDF). Diabetes. 62 (6): 2015–25. doi:10.2337/db12-1562. PMC 3661616. PMID 23349481.
- Harris, Heather A. (2007). "Estrogen Receptor-β: Recent Lessons fromin Vivo Studies". Molecular Endocrinology. 21 (1): 1–13. doi:10.1210/me.2005-0459. ISSN 0888-8809. PMID 16556737.
- Lattrich C, Schüler S, Häring J, Skrzypczak M, Ortmann O, Treeck O (2014). "Effects of a combined treatment with tamoxifen and estrogen receptor β agonists on human breast cancer cell lines". Arch. Gynecol. Obstet. 289 (1): 163–71. doi:10.1007/s00404-013-2977-7. PMID 23907354.