droloxifene

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}{{Infobox drug

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| IUPAC_name = 3-[(E)-1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol

| image = Droloxifene.svg

| width = 250

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| routes_of_administration = Oral

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| elimination_half-life = 19–37 hours{{cite book | vauthors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA299|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=158, 299}}{{cite book| vauthors = Manni A |title=Endocrinology of Breast Cancer|url=https://books.google.com/books?id=7DSYBwAAQBAJ&pg=PA298|date=15 January 1999|publisher=Springer Science & Business Media|isbn=978-1-59259-699-7|pages=298–}}

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| CAS_number_Ref =

| CAS_number = 82413-20-5

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| PubChem = 3033767

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| ChemSpiderID_Ref =

| ChemSpiderID = 2298372

| UNII = 0M67U6Z98F

| KEGG = D03911

| ChEBI = 34731

| ChEMBL = 487

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

| SMILES = CC/C(=C(/C1=CC=C(C=C1)OCCN(C)C)\C2=CC(=CC=C2)O)/C3=CC=CC=C3

| StdInChI_Ref =

| StdInChI = 1S/C26H29NO2/c1-4-25(20-9-6-5-7-10-20)26(22-11-8-12-23(28)19-22)21-13-15-24(16-14-21)29-18-17-27(2)3/h5-16,19,28H,4,17-18H2,1-3H3/b26-25+

| StdInChIKey_Ref =

| StdInChIKey = ZQZFYGIXNQKOAV-OCEACIFDSA-N

| synonyms = FK-435; ICI-79280; K-060; K-21060E; RP-60850; 3-Hydroxytamoxifen; 3-OH-TAM

}}

Droloxifene (INN, USAN) (former developmental code names FK-435, ICI-79280, K-060, K-21060E, RP-60850), 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.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA472|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=472–}}{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA106|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=106–}}{{cite book| vauthors = Jordan VC, Furr BJ |title=Hormone Therapy in Breast and Prostate Cancer|url=https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA200|date=5 February 2010|publisher=Springer Science & Business Media|isbn=978-1-59259-152-7|pages=200–}}{{cite web | title = Droloxifene | url = https://adisinsight.springer.com/drugs/800000847 | work = AdisInsight | publisher = Springer Nature Switzerland AG }} It reached phase II and phase III clinical trials for these indications before development was discontinued in 2000.{{cite book| vauthors = Ottow E, Weinmann H |title=Nuclear Receptors as Drug Targets|url=https://books.google.com/books?id=iATfLbPgRugC&pg=PA153|date=8 September 2008|publisher=John Wiley & Sons|isbn=978-3-527-62330-3|pages=153–}} The drug was found to be significantly less effective than tamoxifen in the treatment of breast cancer in two phase III clinical trials.{{cite book| vauthors = Devita VT, Hellman S, Rosenberg SA |title=Progress in Oncology 2003|url=https://books.google.com/books?id=4ipsRFlwlx0C&pg=PA217|date=1 April 2003|publisher=Jones & Bartlett Learning|isbn=978-0-7637-2064-3|pages=217–}}

Droloxifene is an analogue of tamoxifen, specifically 3-hydroxytamoxifen, but has been said to have 10- to 60-fold increased affinity for the estrogen receptor{{cite book| vauthors = Missailidis S |title=Anticancer Therapeutics|url=https://books.google.com/books?id=BQOWmnxcaMwC&pg=PA165|date=13 October 2008|publisher=John Wiley & Sons|isbn=978-0-470-69703-0|pages=165–}} and reduced partial estrogen agonistic activity.{{cite journal | vauthors = Grese TA, Dodge JA | title = Selective estrogen receptor modulators (SERMs) | journal = Current Pharmaceutical Design | volume = 4 | issue = 1 | pages = 71–92 (76) | date = February 1998 | doi = 10.2174/138161280401221007111005 | pmid = 10197034 | s2cid = 40919336 | url = https://books.google.com/books?id=dg4ropCtzJgC&pg=PA76 }} The affinity of droloxifene for the estrogen receptor ranges from 0.2 to 15.2% relative to estradiol in different studies.{{cite book |vauthors=Wittliff JL, Kerr DA II, Andres SA | year = 2005 | chapter = Estrogens IV: Estrogen-Like Pharmaceuticals | editor = Wexler, P. | title = Encyclopedia of Toxicology, 2nd Edition | volume = Dib-L | pages = 254–258 | publisher = Elsevier | isbn = 978-0-08-054800-5 | chapter-url = https://books.google.com/books?id=dEnbcGW44RYC&pg=PT3318}} For comparison, the ranges are 0.06 to 16% for tamoxifen and 0.1 to 12% for clomifene. Droloxifene causes a dose-dependent decrease in luteinizing hormone and follicle-stimulating hormone levels, indicating that it has antigonadotropic activity, and dose-dependently increases sex hormone-binding globulin levels, indicating that it has estrogenic activity in the liver. Similarly to tamoxifen, droloxifene has partial estrogenic effects in the uterus.{{cite book| vauthors = Morrow M, Jordan VC |title=Managing Breast Cancer Risk|url=https://books.google.com/books?id=HXKibhaF5lMC&pg=PA193|year=2003|publisher=PMPH-USA|isbn=978-1-55009-260-8|pages=193–}} Unlike tamoxifen, droloxifene does not produce DNA adduct or liver tumors in animals.