Triphenylethylene Explained

Triphenylethylene (TPE) is a simple aromatic hydrocarbon that possesses weak estrogenic activity.^{[1] [2]} Its estrogenic effects were discovered in 1937.^[3] TPE was derived from structural modification of the more potent estrogen diethylstilbestrol, which is a member of the stilbestrol group of nonsteroidal estrogens.^[4]

TPE is the parent compound of a group of nonsteroidal estrogen receptor ligands.^[5] It includes the estrogens chlorotrianisene, desmethylchlorotrianisene, estrobin (DBE), M2613, triphenylbromoethylene, triphenylchloroethylene, triphenyliodoethylene, triphenylmethylethylene; the selective estrogen receptor modulators (SERMs) afimoxifene, brilanestrant, broparestrol, clomifene, clomifenoxide, droloxifene, endoxifen, etacstil, fispemifene, idoxifene, miproxifene, miproxifene phosphate, nafoxidine, ospemifene, panomifene, and toremifene. The antiestrogen ethamoxytriphetol (MER-25) is also closely related, but is technically not a derivative of TPE and is instead a triphenylethanol derivative. The tamoxifen metabolite and aromatase inhibitor norendoxifen is also a TPE derivative. In addition to their estrogenic activity, various TPE derivatives like tamoxifen and clomifene have been found to act as protein kinase C inhibitors.^[6]

The affinity of triphenylethylene for the rat estrogen receptor is about 0.002% relative to estradiol.^{[7] [8]} For comparison, the relative binding affinities of derivatives of triphenylethylene were 1.6% for tamoxifen, 175% for afimoxifene (4-hydroxytamoxifen), 15% for droloxifene, 1.4% for toremifene (4-chlorotamoxifen), 0.72% for clomifene, and 0.72% for nafoxidine.^[9]

See also

• List of SERMs
• Benzothiophene – parent compound for another group of nonsteroidal SERMs that includes raloxifene
• Phenanthrene – parent compound of steroidal estrogens like estradiol
• Chrysene – parent compound of a group of nonsteroidal weak estrogens that includes 2,8-DHHHC and tetrahydrochrysene
• Doisynolic acid – parent compound of a group of nonsteroidal estrogens that includes doisynoestrol
• Allenolic acid – parent compound of a group of nonsteroidal estrogens that includes methallenestril

Notes and References

1. Book: Dragan YP, Pitot HC . The Effect of Triphenylethylene Antiestrogens on Parameters of Multisage Hepatocarcinogenesis in the Rat . Jordan VD, Furr BJ . Hormone Therapy in Breast and Prostate Cancer. https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA95 . 5 February 2010. Springer Science & Business Media. 978-1-59259-152-7. 95–.
2. Book: Maximov PY, McDaniel RE, Jordan VC . Discovery and Pharmacology of Nonsteroidal Estrogens and Antiestrogens . Tamoxifen: Pioneering Medicine in Breast Cancer. https://books.google.com/books?id=p-W5BAAAQBAJ&pg=PA4 . 23 July 2013. Springer Science & Business Media. 978-3-0348-0664-0. 4–.
3. Book: Li JJ . Genesis of Statins . Triumph of the Heart: The Story of Statins. https://books.google.com/books?id=-GPl1PA5EgMC&pg=PA33. 3 April 2009. Oxford University Press, USA. 978-0-19-532357-3. 33–.
4. Book: Avendano C, Menendez JC . Anticancer Drugs that Modulate Hormone Action . Medicinal Chemistry of Anticancer Drugs. https://books.google.com/books?id=VEibBwAAQBAJ&pg=PA87 . 11 June 2015. Elsevier Science. 978-0-444-62667-7. 81-131 (87) . 10.1016/B978-0-444-62649-3.00003-X .
5. Book: Marin F, Barbancho MC . Clinical Pharmacology of Selective Estrogen Receptor Modulators (SERMs). Cano A, Calaf i Alsina J, Duenas-Diez JL . Selective Estrogen Receptor Modulators: A New Brand of Multitarget Drugs. https://books.google.com/books?id=heJDAAAAQBAJ&pg=PA52. 22 September 2006. Springer Science & Business Media. 978-3-540-34742-2. 52–.
6. O'Brian CA, Liskamp RM, Solomon DH, Weinstein IB . Triphenylethylenes: a new class of protein kinase C inhibitors . Journal of the National Cancer Institute . 76 . 6 . 1243–1246 . June 1986 . 3458960 . 10.1093/jnci/76.6.1243 .
7. Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM . 6 . The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands . Toxicological Sciences . 54 . 1 . 138–153 . March 2000 . 10746941 . 10.1093/toxsci/54.1.138 . free .
8. Fang H, Tong W, Shi LM, Blair R, Perkins R, Branham W, Hass BS, Xie Q, Dial SL, Moland CL, Sheehan DM . 6 . Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens . Chemical Research in Toxicology . 14 . 3 . 280–294 . March 2001 . 11258977 . 10.1021/tx000208y .
9. Book: Wittliff JL, Kerr II DA, Andres SA . 2005 . Estrogens IV: Estrogen-Like Pharmaceuticals . Wexler P . Encyclopedia of Toxicology . 2nd . Dib-L . 254–258 . Elsevier . 978-0-08-054800-5 . https://books.google.com/books?id=dEnbcGW44RYC&pg=PT3318 . 10.1016/B0-12-369400-0/01087-5 .