Afimoxifene

Afimoxifene

Afimoxifene is an active metabolite of tamoxifen that is produced in the liver by the cytochrome P450 isoform CYP2D6. It is one of the compounds that can be metabolized by SULT1A1 and SULT1C4, according to a study on oestrogen receptor targeting drugs.From: Chemistry and Pharmacology of Anticancer Drugs [2021], Species-dependent hepatic and intestinal metabolism of selective oestrogen receptor degrader LSZ102 by sulphation and glucuronidation [2022]

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Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021

David E. Thurston, Ilona Pysz

Finally, there have been attempts to administer afimoxifene (4-hydroxy-tamoxifen) by a transdermal route. In the early 2000s, the company Ascend Therapeutics Inc. developed an afimoxifene-containing transdermal gel formulation (TamoGelTM) for application to the surface of the breast for absorption into breast tissue for the treatment of cyclical mastalgia. The concept behind this approach was that transdermal administration might reduce systemic levels of the drug, thereby reducing some of the more problematic side effects of tamoxifen. Despite a report in 2003 that a Phase II clinical trial in 55 female patients in France had demonstrated an equal efficacy to oral tamoxifen in slowing breast cancer growth, the product was not further developed.

Species-dependent hepatic and intestinal metabolism of selective oestrogen receptor degrader LSZ102 by sulphation and glucuronidation

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Published in Xenobiotica, 2022

David Pearson, Yi Jin, Andrea Romeo, Bertrand-Luc Birlinger, Hilmar Schiller, Yan Ji, Mithat Gunduz, Daniela Baldoni, Markus Walles

A study evaluating the SULTs that metabolise oestrogen receptor targeting drugs found that all four investigated compounds (afimoxifene, endoxifen, raloxifene, and fulvestrant), were metabolised by SULT1A1 and SULT1C4, plus other compound-specific SULTs (Hui et al. 2015). Both SULT1A1 and SULT1C4 are expressed in liver and intestine, and all four compounds were shown to be metabolised by cytosol from liver and intestine cells. All four compounds contain a phenol moiety as conjugation site, although only raloxifene contains the full hydroxybenzothiazole structure which is present in LSZ102.

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Endocrine Therapies

Species-dependent hepatic and intestinal metabolism of selective oestrogen receptor degrader LSZ102 by sulphation and glucuronidation