Ethamoxytriphetol (developmental code name MER-25) is a
syntheticnonsteroidalantiestrogen 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 the
uterus have been observed,[2] so it is not a pure antiestrogen (that is, a
silent antagonist of the
estrogen receptor (ER)) but is, instead, technically a
selective estrogen receptor modulator (SERM).[5] For all intents and purposes, it is a nearly pure antiestrogen, however.[6]
MER-25, a simple
triphenylethanol derivative,[6][4] is closely related structurally to the
triphenylethylene (TPE) group of SERMs, which includes
clomifene and tamoxifen.[2] The drug, a derivative of the
cholesterol-lowering agent
triparanol (MER-29) (which itself was derived from the estrogen
chlorotrianisene (also known as TACE)),[9][11] was originally being studied in animals at
Merrell Dow as a treatment for
coronary artery disease.[4] Its antiestrogenic properties were discovered serendipitously when Leonard Lerner, a
researchendocrinologist at the company who was employed to study nonsteroidal estrogen pharmacology, noted the structural similarity of MER-25 to
estrogenic 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]
The
affinity of ethamoxytriphetol for the rat ER is approximately 0.06% relative to
estradiol.[12][13] For comparison, the affinities of
tamoxifen and
afimoxifene (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.
^
abcdHarper MJ (1968). "Pharmacological Control of Reproduction in Women". Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques. 12: 47–136.
doi:
10.1007/978-3-0348-7065-8_2.
ISBN978-3-0348-7067-2.
PMID4892528.
^
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.