afimoxifene

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = verified

| Watchedfields = verified

| verifiedrevid = 477243306

| IUPAC_name = (Z)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol

| image = Afimoxifene2DACS.svg

| width = 250px

| tradename = TamoGel

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| routes_of_administration = Topical (gel)

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 68392-35-8

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| PubChem = 449459

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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 395987

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 17197F0KYM

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D06551

| ChEBI = 44616

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 489

| synonyms = 4-Hydroxytamoxifen; 4-OHT; 4-HT; OHTAM; TamoGel

| C=26 | H=29 | N=1 | O=2

| SMILES = CC\C(c1ccccc1)=C(c2ccc(OCCN(C)C)cc2)/c3ccc(O)cc3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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-

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = TXUZVZSFRXZGTL-QPLCGJKRSA-N

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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.{{Cite web |title=Afimoxifene - BHR Pharma |url=http://adisinsight.springer.com/drugs/800019175 |website=AdisInsight |publisher=Springer Nature Switzerland AG}}{{Cite journal |vauthors=Desta Z, Ward BA, Soukhova NV, Flockhart DA |date=September 2004 |title=Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6 |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=310 |issue=3 |pages=1062–1075 |doi=10.1124/jpet.104.065607 |pmid=15159443 |s2cid=21413981}}{{Cite web |title=Statement on a nonproprietary name adopted by the USAN council: Afimoxifene |url=http://www.ama-assn.org/ama1/pub/upload/mm/365/afimoxifene.pdf |access-date=2008-03-26 |publisher=American Medical Association}} The drug is under development under the tentative brand name TamoGel as a topical gel for the treatment of hyperplasia of the breast.{{Cite book |title=Management of Breast Diseases |vauthors=Goyal A, Mansel RE |date=16 November 2016 |publisher=Springer |isbn=978-3-319-46356-8 |veditors=Jatoi I, Rody A |pages=77– |chapter=Mastalgia |chapter-url=https://books.google.com/books?id=f9iCDQAAQBAJ&pg=PA77}} It has completed a phase II clinical trial for cyclical mastalgia,{{Cite journal |vauthors=Mansel R, Goyal A, Nestour EL, Masini-Etévé V, O'Connell K |date=December 2007 |title=A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women |journal=Breast Cancer Research and Treatment |volume=106 |issue=3 |pages=389–397 |doi=10.1007/s10549-007-9507-x |pmid=17351746 |s2cid=22382077}} but further studies are required before afimoxifene can be approved for this indication and marketed.

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).{{Cite journal |vauthors=Prossnitz ER, Arterburn JB |date=July 2015 |title=International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators |journal=Pharmacological Reviews |volume=67 |issue=3 |pages=505–540 |doi=10.1124/pr.114.009712 |pmc=4485017 |pmid=26023144}} 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.{{Cite book |url=https://books.google.com/books?id=ZabQAQAAQBAJ&pg=PT271 |title=Hormones and Cancer: Breast and Prostate, An Issue of Endocrinology and Metabolism Clinics of North America |vauthors=Levine AC |date=3 October 2011 |publisher=Elsevier Health Sciences |isbn=978-1-4557-1239-7 |pages=271–}}{{Cite book |title=Endocrine Disruptors in the Environment |vauthors=Khetan SK |date=23 May 2014 |publisher=Wiley |isbn=978-1-118-89115-5 |pages=104– |chapter=Anti-Androgenic Chemicals |chapter-url=https://books.google.com/books?id=s2ajAwAAQBAJ&pg=PT104}}{{Cite journal |vauthors=Ariazi EA, Jordan VC |date=2006 |title=Estrogen-related receptors as emerging targets in cancer and metabolic disorders |journal=Current Topics in Medicinal Chemistry |volume=6 |issue=3 |pages=203–215 |doi=10.2174/1568026610606030203 |pmid=16515477}}