List of selective estrogen receptor modulators

This is a list of selective estrogen receptor modulators (SERMs).

Tamoxifen, a triphenylethylene derivative and the most well-known and widely used SERM.

Approved

SERMs that have been approved for medical use include anordrin (+mifepristone (Zi Yun)), bazedoxifene (+conjugated estrogens (Duavee)), broparestrol (Acnestrol), clomifene (Clomid), cyclofenil (Sexovid), lasofoxifene (Fablyn), ormeloxifene (Centron, Novex, Novex-DS, Sevista), ospemifene (Osphena; deaminohydroxytoremifene), raloxifene (Evista), tamoxifen (Nolvadex), and toremifene (Fareston; 4-chlorotamoxifen).^[1]

Clinical trials

SERMs that are currently under development and in clinical trials include acolbifene, afimoxifene (4-hydroxytamoxifen; metabolite of tamoxifen), elacestrant, enclomifene ((E)-clomifene), endoxifen (4-hydroxy-N-desmethyltamoxifen; metabolite of tamoxifen), and zuclomifene ((Z)-clomifene).^[2]

Non-approved

SERMs that have not been approved for medical use include arzoxifene, brilanestrant, clomifenoxide (clomiphene N-oxide; metabolite of clomifene),^[3] droloxifene (3-hydroxytamoxifen), etacstil, fispemifene, GW-7604 (4-hydroxyetacstil; metabolite of etacstil), idoxifene (pyrrolidino-4-iodotamoxifen), levormeloxifene ((L)-ormeloxifene), miproxifene, nafoxidine, nitromifene (CI-628), NNC 45-0095, panomifene, pipendoxifene (ERA-923), trioxifene, and zindoxifene (D-16726).^{[4][1][5][6][7]}

Sivifene (A-007) was initially thought to be a SERM due to its structural similarity to tamoxifen but it was subsequently found not to bind to the estrogen receptor (ER).^[8] Tesmilifene (DPPE; YMB-1002, BMS-217380-01) is also structurally related to tamoxifen but similarly does not bind to the ER and is not a SERM.^[9][10]

Structure

SERMs can be variously classified structurally as triphenylethylenes (tamoxifen, clomifene, toremifene, droloxifene, idoxifene, ospemifene, fispemifene, afimoxifene, others), benzothiophenes (raloxifene, arzoxifene), indoles (bazedoxifene, zindoxifene, pipendoxifene), tetrahydronaphthalenes (lasofoxifene, nafoxidine), and benzopyrans (acolbifene, ormeloxifene, levormeloxifene).^[11][12][13]

References

1. Pinkerton, JoAnn V.; Thomas, Semara (2014). "Use of SERMs for treatment in postmenopausal women". The Journal of Steroid Biochemistry and Molecular Biology. 142: 142–154. doi:10.1016/j.jsbmb.2013.12.011. ISSN 0960-0760. PMID 24373794. S2CID 24196362.
2. "Home - AdisInsight". adisinsight.springer.com.
3. Analytical Profiles of Drug Substances and Excipients. Academic Press. 20 March 1998. pp. 112–113. ISBN 978-0-08-086120-3.
4. World Health Organization (2013), The use of stems in the selection of International Nonproprietary Names (INN)for pharmaceutical substances (PDF)
5. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. ISBN 978-1-4757-2085-3.
6. I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. ISBN 978-94-011-4439-1.
7. Taylor, Hugh S. (2009). "Designing the ideal selective estrogen receptor modulator-an achievable goal?". Menopause. 16 (3): 609–615. doi:10.1097/gme.0b013e3181906fa3. ISSN 1072-3714. PMC 3107842. PMID 19182697.
8. Eilender, David; LoRusso, Patricia; Thomas, Leonard; McCormick, Catherine; Rodgers, Andrew H.; Hooper, Catherine L.; Tornyos, Karl; Krementz, Edward T.; Parker, Steven; Morgan, Lee Roy (2005). "4,4′-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007): a topical treatment for cutaneous metastases from malignant cancers". Cancer Chemotherapy and Pharmacology. 57 (6): 719–726. doi:10.1007/s00280-005-0124-2. ISSN 0344-5704. PMID 16184382. S2CID 10830366.
9. Brandes LJ (2008). "N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer". Hum Exp Toxicol. 27 (2): 143–7. doi:10.1177/0960327108090751. PMID 18480139. S2CID 20966915.
10. Brandes LJ, Hermonat MW (1984). "A diphenylmethane derivative specific for the antiestrogen binding site found in rat liver microsomes". Biochem. Biophys. Res. Commun. 123 (2): 724–8. doi:10.1016/0006-291x(84)90289-4. PMID 6548377.
11. John P. Bilezikian; Lawrence G. Raisz; T. John Martin (29 September 2008). Principles of Bone Biology. Academic Press. pp. 891–. ISBN 978-0-08-056875-1.
12. Stuart Silverman; Bo Abrahamsen (29 December 2015). The Duration and Safety of Osteoporosis Treatment: Anabolic and Antiresorptive Therapy. Springer. pp. 24–. ISBN 978-3-319-23639-1.
13. Atta-ur Rahman; Khurshid Zaman (28 November 2014). Topics in Anti-Cancer Research. Bentham Science Publishers. pp. 559–565. ISBN 978-1-60805-908-9.