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Tamoxifen pp 47–67Cite as

Metabolites of Tamoxifen as the Basis of Drug Development

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Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

By the early 1970s, a number of metabolites of tamoxifen had been identified in animals and following administration to a few patients. The hydroxylated metabolite of tamoxifen, 4-hydroxytamoxifen, proved to be the most interesting. The discovery of its high binding affinity for the estrogen receptor made it a new laboratory tool for all future in vitro studies of antiestrogen action and also provided the clue for all future structure-function relationships studies of new antiestrogens. These compounds would subsequently be developed as selective estrogen receptor modulators (SERMs). Tamoxifen is a prodrug but it is the metabolite 4-hydroxy-N-desmethyltamoxifen or endoxifen that has attracted pharmacogenetic interest. Mutations of the CYP2D6 gene control endoxifen production and have been associated with drug efficacy in some clinical trials.

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  1. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA

    Philipp Y. Maximov, Russell E. McDaniel & V. Craig Jordan

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  1. Philipp Y. Maximov
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  2. Russell E. McDaniel
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Maximov, P.Y., McDaniel, R.E., Jordan, V.C. (2013). Metabolites of Tamoxifen as the Basis of Drug Development. In: Tamoxifen. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0348-0664-0_3

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