Ethamoxytriphetol (developmental code nameMER-25) is asyntheticnonsteroidalantiestrogen that was studied clinically in the late 1950s and early 1960s but was never marketed.[1] MER-25 was first reported in 1958, and was the first antiestrogen to be discovered.[2][3][4] It has been described as "essentially devoid of estrogenic activity" and as having "very low estrogenic activity in all species tested".[1][2] However, some estrogenic effects in theuterus have been observed,[2] so it is not a pure antiestrogen (that is, asilent antagonist of theestrogen receptor (ER)) but is, instead, technically aselective estrogen receptor modulator (SERM).[5] For all intents and purposes, it is a nearly pure antiestrogen, however.[6]
MER-25, a simpletriphenylethanol derivative,[6][4] is closely related structurally to thetriphenylethylene (TPE) group of SERMs, which includesclomifene and tamoxifen.[2] The drug, a derivative of thecholesterol-lowering agenttriparanol (MER-29) (which itself was derived from the estrogenchlorotrianisene (also known as TACE)),[9][11] was originally being studied in animals atMerrell Dow as a treatment forcoronary artery disease.[4] Its antiestrogenic properties were discovered serendipitously when Leonard Lerner, aresearchendocrinologist at the company who was employed to study nonsteroidal estrogen pharmacology, noted the structural similarity of MER-25 toestrogenic TPE derivatives and decided to test the compound for estrogenicity.[4] Instead of the expected estrogenic effects however, Lerner found that MER-25 blocked the effects of estrogens.[4] Lerner subsequently went on to be involved in the discovery of clomifene, the first potently antiestrogenic TPE derivative to be characterized.[4] The structure of clomifene is similar to that of its predecessor, MER-25.[4][7] Clomifene is about 10-fold more potent as an antiestrogen than MER-25.[7]
Theaffinity of ethamoxytriphetol for the rat ER is approximately 0.06% relative toestradiol.[12][13] For comparison, the affinities oftamoxifen andafimoxifene (4-hydroxytamoxifen) for the rat ER relative to estradiol were 1% and 252%, respectively.[12][13]
Footnotes:a = "The particular advantage of this drug is the low incidence of troublesome side effects (25)." "Side effects were usually trivial (26)."Sources:[14][15]
^abWakeling AE (5 February 2010)."Pure Antiestrogen". In Jorden VC, Furr BJ (eds.).Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 4, 161.ISBN978-1-59259-152-7.
^abChander SK, Sahota SS, Evans TR, Luqmani YA (December 1993). "The biological evaluation of novel antioestrogens for the treatment of breast cancer".Crit Rev Oncol Hematol.15 (3):243–69.doi:10.1016/1040-8428(93)90044-5.PMID8142059.
