NAFOXIDINE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H31NO2
Molecular Weight	425.5619
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C2C(CCC(C3=CC=CC=C3)=C2C4=CC=C(OCCN5CCCC5)C=C4)=C1

InChI

InChIKey=JEYWNNAZDLFBFF-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C29H31NO2
Molecular Weight	425.5619
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/991075 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=39309 | https://www.ncbi.nlm.nih.gov/pubmed/8702220

Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. It has been used effectively in the treatment of breast cancer patients. Nafoxidine competes with endogenous estrogen for binding to specific estrogen receptors. This agent also inhibits angiogenesis in some tissues by blocking the effects of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF); paradoxically, it may enhance angiogenesis in uterine tissue. Nafoxidine also induces oxidative stress, protein kinase C and calcium signaling.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor 72 Target ID: CHEMBL2094114 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9685230 \| https://www.ncbi.nlm.nih.gov/pubmed/7297482 \| https://www.ncbi.nlm.nih.gov/pubmed/9048584	Antagonist 2849		40.9 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/991075 https://www.ncbi.nlm.nih.gov/pubmed/1095121	Primary		Phase I 438	Unknown Approved Use Unknown
Renal carcinoma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6454485	Primary		Phase III 665	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	Disc. AE: Ichthyosis... Other AEs: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Ichthyosis Other AEs: Nausea (grade 3, 2%) Vomiting (grade 3, 2%) Hypercalcaemia (2%) Serum transaminase increased (2%) Thrombophlebitis leg (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4561336	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4561336	Disc. AE: Hypercalcemia... AEs leading to discontinuation/dose reduction: Hypercalcemia (4.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/4561336

AEs

AE	Significance	Dose	Population
Hypercalcaemia	2%	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Serum transaminase increased	2%	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Thrombophlebitis leg	2%	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Ichthyosis	Disc. AE	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Nausea	grade 3, 2%	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Vomiting	grade 3, 2%	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1095121	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1095121
Hypercalcemia	4.3% Disc. AE	60 mg 3 times / day multiple, oral Studied dose Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4561336	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4561336

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	10755	http://www.achemblock.com/catalogsearch/result/?q=10755
AK Scientific	3697AL	https://aksci.com/item_detail.php?cat=3697AL
Angene	AGN-PC-0QDKPN	http://www.angenechemical.com/productshow/AGN-PC-0QDKPN.html
AstaTech	42119	http://astatechinc.com/CPSResult.php?CRNO=42119
BOC Sciences	1845-11-0	http://www.bocsci.com/description.asp?cas=1845-11-0
BOC Sciences	1847-63-8	http://www.bocsci.com/description.asp?cas=1847-63-8
Combi-Blocks	QJ-8061	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-8061
eMolecules	300557368	https://orderbb.emolecules.com/search/#?query=300557368
eMolecules	36772485	https://orderbb.emolecules.com/search/#?query=36772485
eMolecules	48542635	https://orderbb.emolecules.com/search/#?query=48542635
MuseChem	M120421	https://www.musechem.com/product/M120421.html
MuseChem	R056483	https://www.musechem.com/product/R056483.html
ShangHai Biochempartner	BCP07493	http://www.biochempartner.com/search_BCP07493
Toronto Research Chemicals	A613195	https://www.trc-canada.com/product-detail/?CatNum=A613195
Toronto Research Chemicals	N212800	https://www.trc-canada.com/product-detail/?CatNum=N212800

PubMed

Title	Date	PubMed
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.	2015-02	25349334
Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1/ mice with collagen-induced chronic arthritis.	2010-12-16	21159208
Granulosa cell tumor of the ovary and antecedent of adjuvant tamoxifen use for breast cancer.	2010-08-12	20704728
A human brainstem glioma xenograft model enabled for bioluminescence imaging.	2010-01	19585223
The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis.	2007	18044075
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006-11	16497524
Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.	2006-07-11	16834778
Diversity of Cl(-) channels.	2006-01	16314923
Induction and inhibition of oocyte maturation by EDCs in zebrafish.	2005-12-09	16336677
Comparison of the antiproliferative properties of antiestrogenic drugs (nafoxidine and clomiphene) on glioma cells in vitro.	2004-08	15289732
Role of protein kinase C-dependent signaling pathways in the antiangiogenic properties of nafoxidine.	2004-07-28	15274349
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003-10	14565775
Multifactorial activities of nonsteroidal antiestrogens against leukemia.	2003	14585326
Tracing the origins of COX-2 inhibitors' structures.	2002-08	12173976
Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells.	2002-05-24	12004198
Genistein effects on growth and cell cycle of Candida albicans.	2001-04-05	11287745
Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine.	2001-01	11156570
Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.	1997-03	9048584
Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors.	1996-05-01	8702220

Patents

Sample Use Guides

In Vivo Use Guide

Most breast cancer patients have been treated with a dose of 60 mg three times a day.

Route of Administration: Oral

In Vitro Use Guide

In vitro nafoxidine competitively inhibits binding of [3H]oestradiol in nuclear extracts. The Ki for the inhibition is 43 nM, which indicates an affinity of nafoxidine for the binding protein about 4% of that of oestradiol.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:11:26 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:26 GMT 2025`
Record UNII	4RIY10WM82
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NAFOXIDINE

Official Name

English

nafoxidine [INN]

Preferred Name

English

Nafoxidine [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1821