NAFOXIDINE

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=CC2=C(C=C1)C(C3=CC=C(OCCN4CCCC4)C=C3)=C(CC2)C5=CC=CC=C5

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 75 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 2778		40.9 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/991075 https://www.ncbi.nlm.nih.gov/pubmed/1095121	Primary		Phase I 428	Unknown Approved Use Unknown
Renal carcinoma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6454485	Primary		Phase III 656	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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713	Disc. AE: Ichthyosis... Other AEs: Serum transaminase increased, Nausea... AEs leading to discontinuation/dose reduction: Ichthyosis Other AEs: Serum transaminase increased (2%) Nausea (grade 3, 2%) Vomiting (grade 3, 2%) Hypercalcaemia (2%) Thrombophlebitis leg (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.388	unhealthy, ADULT n = 23 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/4561336 Page: p.388	Disc. AE: Hypercalcemia... AEs leading to discontinuation/dose reduction: Hypercalcemia (4.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/4561336 Page: p.388

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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.713	unhealthy, ADULT n = 49 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/1095121 Page: p.713
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 Page: p.388	unhealthy, ADULT n = 23 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 23 Sources: https://pubmed.ncbi.nlm.nih.gov/4561336 Page: p.388

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
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
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

PubMed

Title	Date	PubMed
Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors.	1996 May-Jun	8702220
Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.	1997 Mar	9048584
Inhibition of volume-regulated anion channels in cultured endothelial cells by the anti-oestrogens clomiphene and nafoxidine.	2001 Jan	11156570
Genistein effects on growth and cell cycle of Candida albicans.	2001 Mar-Apr	11287745
Tracing the origins of COX-2 inhibitors' structures.	2002 Aug	12173976
Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells.	2002 May 24	12004198
Multifactorial activities of nonsteroidal antiestrogens against leukemia.	2003	14585326
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003 Oct	14565775
Comparison of the antiproliferative properties of antiestrogenic drugs (nafoxidine and clomiphene) on glioma cells in vitro.	2004 Aug	15289732
Role of protein kinase C-dependent signaling pathways in the antiangiogenic properties of nafoxidine.	2004 May-Jun	15274349
Induction and inhibition of oocyte maturation by EDCs in zebrafish.	2005 Dec 9	16336677
Diversity of Cl(-) channels.	2006 Jan	16314923
Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.	2006 Jul 11	16834778
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators), and parathyroid hormone on bone remodeling in osteoporosis.	2007	18044075
Granulosa cell tumor of the ovary and antecedent of adjuvant tamoxifen use for breast cancer.	2010 Aug 12	20704728
Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1/ mice with collagen-induced chronic arthritis.	2010 Dec 16	21159208
A human brainstem glioma xenograft model enabled for bioluminescence imaging.	2010 Jan	19585223
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 Feb	25349334

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 `Fri Dec 15 15:52:04 GMT 2023` Edited by `admin` on `Fri Dec 15 15:52:04 GMT 2023`
Record UNII	4RIY10WM82
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NAFOXIDINE

Official Name

English

Nafoxidine [WHO-DD]

Common Name

English

nafoxidine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1821