:Nafoxidine

{{short description|Chemical compound}}

{{Drugbox

| Verifiedfields =

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| IUPAC_name = 1-[2-[4-(6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine

| image = Nafoxidine.svg

| width = 200px

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| routes_of_administration = By mouth

| bioavailability =

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| CAS_number_Ref =

| CAS_number = 1845-11-0

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| ATC_prefix = None

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| PubChem = 4416

| IUPHAR_ligand = 4263

| DrugBank_Ref =

| DrugBank =

| ChemSpiderID_Ref =

| ChemSpiderID = 4263

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

| UNII = 4RIY10WM82

| KEGG = C14212

| ChEBI = 34881

| ChEMBL = 28211

| synonyms = U-11,000A; NSC-70735

| C=29 | H=31 | N=1 | O=2

| SMILES = COC1=CC2=C(C=C1)C(=C(CC2)C3=CC=CC=C3)C4=CC=C(C=C4)OCCN5CCCC5

| StdInChI_Ref =

| StdInChI = 1S/C29H31NO2/c1-31-26-14-16-28-24(21-26)11-15-27(22-7-3-2-4-8-22)29(28)23-9-12-25(13-10-23)32-20-19-30-17-5-6-18-30/h2-4,7-10,12-14,16,21H,5-6,11,15,17-20H2,1H3

| StdInChIKey_Ref =

| StdInChIKey = JEYWNNAZDLFBFF-UHFFFAOYSA-N

}}

Nafoxidine ({{Abbrlink|INN|International Nonproprietary Name}}; developmental code names U-11,000A) or nafoxidine hydrochloride ({{Abbrlink|USAN|United States Adopted Name}}) is a nonsteroidal selective estrogen receptor modulator (SERM) or partial antiestrogen of the triphenylethylene group that was developed for the treatment of advanced breast cancer by Upjohn in the 1970s but was never marketed.{{Cite book |url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA848 |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |vauthors=Elks J |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=848–}}{{Cite book |url=https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA95 |title=Hormone Therapy in Breast and Prostate Cancer |vauthors=Craig JV, Furr BJ |date=5 February 2010 |publisher=Springer Science & Business Media |isbn=978-1-59259-152-7 |pages=95–96}}{{Cite book |url=https://books.google.com/books?id=dhs_CgAAQBAJ&pg=PA361 |title=Molecular Therapies of Cancer |vauthors=Weber GF |date=22 July 2015 |publisher=Springer |isbn=978-3-319-13278-5 |pages=361–}} It was developed at around the same time as tamoxifen and clomifene, which are also triphenylethylene derivatives. The drug was originally synthesized by the fertility control program at Upjohn as a postcoital contraceptive, but was subsequently repurposed for the treatment of breast cancer.{{Cite journal |vauthors=McDaniel RE, Maximov PY, Jordan VC |date=2013 |title=Estrogen-mediated mechanisms to control the growth and apoptosis of breast cancer cells: a translational research success story |url=https://books.google.com/books?id=vBvzF6HQ4-QC&pg=PA32 |journal=Vitamins and Hormones |volume=93 |pages=1–49 |doi=10.1016/B978-0-12-416673-8.00007-1 |pmid=23810002}} Nafoxidine was assessed in clinical trials in the treatment of breast cancer and was found to be effective.{{Cite journal |vauthors=Coelingh Bennink HJ, Verhoeven C, Dutman AE, Thijssen J |date=January 2017 |title=The use of high-dose estrogens for the treatment of breast cancer |journal=Maturitas |volume=95 |pages=11–23 |doi=10.1016/j.maturitas.2016.10.010 |pmid=27889048 |doi-access=free}}{{Cite journal |vauthors=Steinbaum FL, De Jager RL, Krakoff IH |year=1978 |title=Clinical trial of nafoxidine in advanced breast cancer |journal=Medical and Pediatric Oncology |volume=4 |issue=2 |pages=123–126 |doi=10.1002/mpo.2950040207 |pmid=661750}} However, it produced side effects including ichthyosis, partial hair loss, and phototoxicity of the skin in almost all patients, and this resulted in the discontinuation of its development.{{Cite book |url=https://books.google.com/books?id=VddUa-2cp-YC&pg=PA95 |title=Hormones and Vitamins in Cancer Treatment |vauthors=Lupulescu A |date=24 October 1990 |publisher=CRC Press |isbn=978-0-8493-5973-6 |pages=95–}}

Nafoxidine is a long-acting estrogen receptor ligand, with a nuclear retention in the range of 24 to 48 hours or more.{{Cite journal |vauthors=Hammond CB, Maxson WS |date=January 1982 |title=Current status of estrogen therapy for the menopause |journal=Fertility and Sterility |volume=37 |issue=1 |pages=5–25 |doi=10.1016/S0015-0282(16)45970-4 |pmid=6277697}}

{{Comparison of early clinical experience with antiestrogens for advanced breast cancer}}