Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. See also Raloxifene.
Raloxifene is a selective estrogen receptor modulator (SERM) (see Estrogen receptor) and hence is a mixed agonist and antagonist of the estrogen receptor (ER) in different tissues.[1] It has estrogenic activity in some tissues, such as bone and the liver, and antiestrogenic activity in other tissues, such as the breasts and uterus.[1] Its affinity (Kd) for the ERα is approximately 50 pM, which is similar to that of estradiol.[2] Relative to estradiol (see Estrogens), raloxifene has been reported to possess about 8 to 34% of the affinity for the ERα and 0.5 to 76% of the affinity for the ERβ.[3][4] Raloxifene acts as a partial agonist of the ERα and as a pure antagonist of the ERβ.[5][6] In contrast to the classical ERs, raloxifene is an agonist of the G protein-coupled estrogen receptor (GPER) (EC50 = 10–100 nM), a membrane estrogen receptor.[7][8]
Estrogen receptor α complexed with raloxifene (1err).
Raloxifene binding site. Water molecule shown as red sphere.
Estrogen receptor α complexed with raloxifene and a corepressor peptide
Click here to see the difference between conformations of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from Gallery of Morphs of the Yale Morph Server).
- ↑ 1.0 1.1 "Raloxifene Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 22 March 2019.
- ↑ Goldstein SR, Siddhanti S, Ciaccia AV, Plouffe L Jr. A pharmacological review of selective oestrogen receptor modulators. Hum Reprod Update. 2000 May-Jun;6(3):212-24. PMID:10874566 doi:10.1093/humupd/6.3.212
- ↑ Weatherman RV, Clegg NJ, Scanlan TS. Differential SERM activation of the estrogen receptors (ERalpha and ERbeta) at AP-1 sites. Chem Biol. 2001 May;8(5):427-36. PMID:11358690 doi:10.1016/s1074-5521(01)00025-4
- ↑ Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, Nicolas JC, Cavaillès V, Balaguer P. Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta. Biochem Pharmacol. 2006 May 14;71(10):1459-69. PMID:16554039 doi:10.1016/j.bcp.2006.02.002
- ↑ Greene GL, Shiau AK, Nettles KW. A structural explanation for ERalpha/ERbeta SERM discrimination. Ernst Schering Res Found Workshop. 2004;(46):33-45. PMID:15248503 doi:10.1007/978-3-662-05386-7_3
- ↑ Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S. Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol. 1998 Jul;54(1):105-12. PMID:9658195 doi:10.1124/mol.54.1.105
- ↑ Prossnitz ER, Arterburn JB. International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators. Pharmacol Rev. 2015 Jul;67(3):505-40. PMID:26023144 doi:10.1124/pr.114.009712
- ↑ Petrie WK, Dennis MK, Hu C, Dai D, Arterburn JB, Smith HO, Hathaway HJ, Prossnitz ER. G protein-coupled estrogen receptor-selective ligands modulate endometrial tumor growth. Obstet Gynecol Int. 2013;2013:472720. PMID:24379833 doi:10.1155/2013/472720
