Afimoxifene

Last updated
Afimoxifene
Afimoxifene2DACS.svg
Clinical data
Trade names TamoGel
Other names4-Hydroxytamoxifen; 4-OHT; 4-HT; OHTAM; TamoGel
Routes of
administration
Topical (gel)
Identifiers
  • (Z)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.163.120 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C26H29NO2
Molar mass 387.523 g·mol−1
3D model (JSmol)
  • CC\C(c1ccccc1)=C(c2ccc(OCCN(C)C)cc2)/c3ccc(O)cc3
  • InChI=1S/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25- Yes check.svgY
  • Key:TXUZVZSFRXZGTL-QPLCGJKRSA-N Yes check.svgY
   (verify)

Afimoxifene, also known as 4-hydroxytamoxifen (4-OHT) and by its tentative brand name TamoGel, is a selective estrogen receptor modulator (SERM) of the triphenylethylene group and an active metabolite of tamoxifen. [1] [2] [3] The drug is under development under the tentative brand name TamoGel as a topical gel for the treatment of hyperplasia of the breast. [1] [4] It has completed a phase II clinical trial for cyclical mastalgia, [5] but further studies are required before afimoxifene can be approved for this indication and marketed. [4]

Contents

Afimoxifene is a SERM and hence acts as a tissue-selective agonist–antagonist of the estrogen receptors ERα and ERβ with mixed estrogenic and antiestrogenic activity depending on the tissue. It is also an agonist of the G protein-coupled estrogen receptor (GPER) with relatively low affinity (100–1,000  nM, relative to 3–6 nM for estradiol). [6] In addition to its estrogenic and antiestrogenic activity, afimoxifene has been found to act as an antagonist of the estrogen-related receptors (ERRs) ERRβ and ERRγ. [7] [8] [9]

See also

Related Research Articles

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<span class="mw-page-title-main">Tamoxifen</span> Medication

Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome. Tamoxifen is typically taken daily by mouth for five years for breast cancer.

<span class="mw-page-title-main">Estrogen receptor</span> Proteins activated by the hormone estrogen

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<span class="mw-page-title-main">Arzoxifene</span> Chemical compound

Arzoxifene is a selective estrogen receptor modulator (SERM) of the benzothiophene group which was never marketed. It is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen nitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.

<span class="mw-page-title-main">Triphenylethylene</span> Chemical compound

Triphenylethylene (TPE) is a simple aromatic hydrocarbon that possesses weak estrogenic activity. Its estrogenic effects were discovered in 1937. TPE was derived from structural modification of the more potent estrogen diethylstilbestrol, which is a member of the stilbestrol group of nonsteroidal estrogens.

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<span class="mw-page-title-main">Etacstil</span> Chemical compound

Etacstil is an orally active, nonsteroidal, combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) that was developed for the treatment of estrogen receptor-positive breast cancer. It was shown to overcome antiestrogen resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties. Etacstil is a tamoxifen derivative and one of the first drugs to overcome tamoxifen-resistance. It is the predecessor of GW-7604, of which etacstil is a prodrug. This is analogous to the case of tamoxifen being a prodrug of afimoxifene (4-hydroxytamoxifen).

<span class="mw-page-title-main">Endoxifen</span> Chemical compound

Endoxifen, also known as 4-hydroxy-N-desmethyltamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group as well as a protein kinase C (PKC) inhibitor. It is under development for the treatment of estrogen receptor-positive breast cancer and for the treatment of mania in bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Droloxifene</span> Chemical compound

Droloxifene, also known as 3-hydroxytamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group that was developed originally in Germany and later in Japan for the treatment of breast cancer, osteoporosis in men and postmenopausal women, and cardiovascular disorders but was abandoned and never marketed. It reached phase II and phase III clinical trials for these indications before development was discontinued in 2000. The drug was found to be significantly less effective than tamoxifen in the treatment of breast cancer in two phase III clinical trials.

<span class="mw-page-title-main">Norendoxifen</span> Chemical compound

Norendoxifen, also known as 4-hydroxy-N,N-didesmethyltamoxifen, is a nonsteroidal aromatase inhibitor (AI) of the triphenylethylene group that was never marketed.

<i>N</i>-Desmethyltamoxifen Chemical compound

N-Desmethyltamoxifen is a major metabolite of tamoxifen, a selective estrogen receptor modulator (SERM). N-Desmethyltamoxifen is further metabolized into endoxifen (4-hydroxy-N-desmethyltamoxifen), which is thought to be the major active form of tamoxifen in the body. In one study, N-desmethyltamoxifen had an affinity for the estrogen receptor of 2.4% relative to estradiol. For comparison, tamoxifen, endoxifen, and afimoxifene (4-hydroxytamoxifen) had relative binding affinities of 2.8%, 181%, and 181%, respectively.

References

  1. 1 2 "Afimoxifene - BHR Pharma". AdisInsight. Springer Nature Switzerland AG.
  2. Desta Z, Ward BA, Soukhova NV, Flockhart DA (September 2004). "Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6". The Journal of Pharmacology and Experimental Therapeutics. 310 (3): 1062–1075. doi:10.1124/jpet.104.065607. PMID   15159443. S2CID   21413981.
  3. "Statement on a nonproprietary name adopted by the USAN council: Afimoxifene" (PDF). American Medical Association. Retrieved 2008-03-26.
  4. 1 2 Goyal A, Mansel RE (16 November 2016). "Mastalgia". In Jatoi I, Rody A (eds.). Management of Breast Diseases. Springer. pp. 77–. ISBN   978-3-319-46356-8.
  5. Mansel R, Goyal A, Nestour EL, Masini-Etévé V, O'Connell K (December 2007). "A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women". Breast Cancer Research and Treatment. 106 (3): 389–397. doi:10.1007/s10549-007-9507-x. PMID   17351746. S2CID   22382077.
  6. Prossnitz ER, Arterburn JB (July 2015). "International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators". Pharmacological Reviews. 67 (3): 505–540. doi:10.1124/pr.114.009712. PMC   4485017 . PMID   26023144.
  7. Levine AC (3 October 2011). Hormones and Cancer: Breast and Prostate, An Issue of Endocrinology and Metabolism Clinics of North America. Elsevier Health Sciences. pp. 271–. ISBN   978-1-4557-1239-7.
  8. Khetan SK (23 May 2014). "Anti-Androgenic Chemicals". Endocrine Disruptors in the Environment. Wiley. pp. 104–. ISBN   978-1-118-89115-5.
  9. Ariazi EA, Jordan VC (2006). "Estrogen-related receptors as emerging targets in cancer and metabolic disorders". Current Topics in Medicinal Chemistry. 6 (3): 203–215. doi:10.2174/1568026610606030203. PMID   16515477.