Triphenylethylene

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]

Triphenylethylene

Identifiers
IUPAC name 1,1',1''-(Ethene-1,1,2-triyl)tribenzene
CAS Number	58-72-0 Y
PubChem CID	6025
ChemSpider	5803
UNII	S4ZLZ1K74B
CompTox Dashboard (EPA)	DTXSID3022320
ECHA InfoCard	100.000.359
Chemical and physical data
Formula	C20H16
Molar mass	256.348 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC=C(C=C1)C=C(C2=CC=CC=C2)C3=CC=CC=C3
InChI InChI=1S/C20H16/c1-4-10-17(11-5-1)16-20(18-12-6-2-7-13-18)19-14-8-3-9-15-19/h1-16H Key:MKYQPGPNVYRMHI-UHFFFAOYSA-N

TPE is the parent compound of a group of nonsteroidal estrogen receptor ligands.^[1][2][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][7][8]

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

References

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