From Wikipedia, the free encyclopedia
Chemical compound
Nafoxidine
Other names U-11,000A; NSC-70735
Routes of administration
By mouth
ATC code
1-[2-[4-(6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine
CAS Number
PubChem
CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.222.756
Formula C 29 H 31 N O 2
Molar mass 425.572 g·mol−1 3D model (
JSmol )
COC1=CC2=C(C=C1)C(=C(CC2)C3=CC=CC=C3)C4=CC=C(C=C4)OCCN5CCCC5
InChI=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
Key:JEYWNNAZDLFBFF-UHFFFAOYSA-N
Nafoxidine (
INN Tooltip International Nonproprietary Name ; developmental code names U-11,000A ) or nafoxidine hydrochloride (
USAN Tooltip 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.
[1]
[2]
[3] It was developed at around the same time as
tamoxifen and
clomifene , which are also triphenylethylene derivatives.
[2] 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.
[4] Nafoxidine was assessed in clinical trials in the treatment of breast cancer and was found to be effective.
[5]
[6] However, it produced
side effects including
ichthyosis , partial
hair loss , and
phototoxicity of the skin in almost all patients,
[5] and this resulted in the discontinuation of its development.
[4]
[7]
Nafoxidine is a long-acting
estrogen receptor
ligand , with a
nuclear retention in the range of 24 to 48 hours or more.
[8]
References
^ Elks J (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 848–.
ISBN
978-1-4757-2085-3 .
^
a
b Craig JV, Furr BJ (5 February 2010).
Hormone Therapy in Breast and Prostate Cancer . Springer Science & Business Media. pp. 95–96.
ISBN
978-1-59259-152-7 .
^ Weber GF (22 July 2015).
Molecular Therapies of Cancer . Springer. pp. 361–.
ISBN
978-3-319-13278-5 .
^
a
b McDaniel RE, Maximov PY, Jordan VC (2013).
"Estrogen-mediated mechanisms to control the growth and apoptosis of breast cancer cells: a translational research success story" . Vitamins and Hormones . 93 : 1–49.
doi :
10.1016/B978-0-12-416673-8.00007-1 .
PMID
23810002 .
^
a
b Coelingh Bennink HJ, Verhoeven C, Dutman AE, Thijssen J (January 2017).
"The use of high-dose estrogens for the treatment of breast cancer" . Maturitas . 95 : 11–23.
doi :
10.1016/j.maturitas.2016.10.010 .
PMID
27889048 .
^ Steinbaum FL, De Jager RL, Krakoff IH (1978). "Clinical trial of nafoxidine in advanced breast cancer". Medical and Pediatric Oncology . 4 (2): 123–126.
doi :
10.1002/mpo.2950040207 .
PMID
661750 .
^ Lupulescu A (24 October 1990).
Hormones and Vitamins in Cancer Treatment . CRC Press. pp. 95–.
ISBN
978-0-8493-5973-6 .
^ Hammond CB, Maxson WS (January 1982). "Current status of estrogen therapy for the menopause". Fertility and Sterility . 37 (1): 5–25.
doi :
10.1016/S0015-0282(16)45970-4 .
PMID
6277697 .
^ Jensen EV, Jordan VC (June 2003).
"The estrogen receptor: a model for molecular medicine" . Clin. Cancer Res . 9 (6): 1980–9.
PMID
12796359 .
^ Howell A, Jordan VC (2013). "Adjuvant Antihormone Therapy". In Craig JV (ed.).
Estrogen Action, Selective Estrogen Receptor Modulators And Women's Health: Progress And Promise . World Scientific. pp. 229–254.
doi :
10.1142/9781848169586_0010 .
ISBN
978-1-84816-959-3 .
ER Tooltip Estrogen receptor
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Mixed (
SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown