HYDROXYFLUTAMIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H11F3N2O4
Molecular Weight	292.2112
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(O)C(=O)NC1=CC=C(C(=C1)C(F)(F)F)[N+]([O-])=O

InChI

InChIKey=YPQLFJODEKMJEF-UHFFFAOYSA-N

InChI=1S/C11H11F3N2O4/c1-10(2,18)9(17)15-6-3-4-8(16(19)20)7(5-6)11(12,13)14/h3-5,18H,1-2H3,(H,15,17)

HIDE SMILES / InChI

Molecular Formula	C11H11F3N2O4
Molecular Weight	292.2112
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/7625752 | https://www.ncbi.nlm.nih.gov/pubmed/28832499 | Lemke, T.L. & Williams, D.A. (2012) Foye's Principles of Medicinal Chemistry, page 1373, retrieved from: https://books.google.ru/books?id=Sd6ot9ul-bUC

Hydroxyflutamide is the major active metabolite of flutamide. Flutamide undergoes extensive first-pass metabolism by CYP1A2 to its metabolite hydroxyflutamide and its hydrolysis product, 3-trifluoromethyl-4-nitroaniline. Hydroxyflutamide is a more powerful antiandrogen in vivo, with higher affinity for the receptor than that of flutamide. Hydroxyflutamide is in phase II clinical trials for the treatment of prostate cancer. However, a drug resistance problem appears after about one year's treatment. Per-residue free energy decomposition analyses indicate that N705, T877, and M895 androgen receptor mutations are vital residues in the agonist/antagonist mechanism of hydroxyflutamide.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 169 Target ID: CHEMBL1871 Sources: http://en.pharmacodia.com/yaodu/html/v1/chemicals/33774f2e84b754ad8973804d0e907534.html \| https://www.ncbi.nlm.nih.gov/pubmed/3713990	Antagonist 2849		0.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Prostate cancer 186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25055161 https://www.ncbi.nlm.nih.gov/pubmed/28832499 http://en.pharmacodia.com/yaodu/html/v1/chemicals/33774f2e84b754ad8973804d0e907534.html	Primary		Phase II 1147	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inhibitor 2252

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 CYP19A1 429	P-gp 2052 MRP1 113

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=17388977	inconclusive [IC50 25.1189 uM]
CYP3A4 2633	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=17388977	no [Activation 25.1189 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144213961	no [IC50 39.8045 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17409513/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007324	no
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12750271/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY103078	https://www.001chemical.com/chem/search?q=DY103078
1PlusChem LLC	1P003HUD	https://www.1pchem.com/search?query=1P003HUD
Aceschem	ACF022416	https://www.aceschem.com/catalog/search.do?q=ACF022416
AK Scientific	X6072	https://aksci.com/item_detail.php?cat=X6072
ApexBio Technology	C4721	https://www.apexbt.com/catalogsearch/result/?q=C4721
Apollo Scientific	PC1193	http://www.apolloscientific.co.uk/chemical_results.php?qstext=PC1193&product_group=%25&search_fieldname=header_search
AstaTech	S10360	http://astatechinc.com/CPSResult.php?CRNO=S10360
BOC Sciences	52806-53-8	http://www.bocsci.com/description.asp?cas=52806-53-8
Capot Chemical	19862	https://www.capotchem.com/search.do?q=19862
Cayman Chemical	15271	http://www.caymanchem.com/app/template/Product.vm/catalog/15271
Chem Scene	CS-W013988	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-W013988
ChemShuttle	102666	https://www.chemshuttle.com/catalogsearch/result/?q=102666
eMolecules	3717966	https://orderbb.emolecules.com/search/#?query=3717966
Enamine	EN300-127735	https://www.enaminestore.com/catalog/EN300-127735
eNovation Chemicals	K31222	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K31222&searchbtn.x=0&searchbtn.y=0
Fluoropharm	OF11982	http://www.fluoropharm.com/product/OF11982.html
Hairui	HR117557	http://www.hairuichem.com/en/product/search.do?q=HR117557
Lab Network	LN01287650	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01287650
Lab Seeker	SC-51166	http://www.labseeker.com/search.php?keywords=SC-51166&category=0
LabSeeker	SC-51166	http://www.labseeker.com/search.php?keywords=SC-51166&category=0
Matrix Scientific	120764	http://www.matrixscientific.com/120764.html
mcule	MCULE-6726517919	https://mcule.com/MCULE-6726517919/
Molcore	MC103078	http://www.molcore.com/CatMC103078.html
MolPort	MolPort-001-771-895	https://www.molport.com/shop/molecule-link/MolPort-001-771-895
MuseChem	R001760	https://www.musechem.com/product/R001760.html
PI Chemicals	PI-17890	http://www.pipharm.com/catalog_products/PI-17890.html
ShangHai Biochempartner	BCP12495	http://www.biochempartner.com/search_BCP12495
SynQuest	4475	http://www.synquestlabs.com/search-result.html?q=4475
SynQuest	4854-3-X0	http://www.synquestlabs.com/search-result.html?q=4854-3-X0
Tetrahedron	TS09186	http://www.thsci.com/search.do?q=TS09186
Toronto Research Chemicals	H942475	https://www.trc-canada.com/product-detail/?CatNum=H942475
Toronto Research Chemicals	T774387	https://www.trc-canada.com/product-detail/?CatNum=T774387
Vesino Industrial Co Ltd	VZ32394	http://www.vsnchem.com/search.do?a=s&psize=20&q=VZ32394

PubMed

Title	Date	PubMed
Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach.	2015-12-15	26485406
The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells.	2015-12	26318274
Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and Its active metabolite hydroxyflutamide using HepG2/C3a microfluidic biochips.	2013-03	22843567
Ligand-independent androgen receptor antagonism caused by the newly developed pesticide pyrifluquinazon (PFQ).	2013-01	23146716
Characterization of steroid hormone receptor activities in 100 hydroxylated polychlorinated biphenyls, including congeners identified in humans.	2011-11-18	21843587
Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets.	2011-06-09	21506597
Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines.	2011-04	21295777
The medial preoptic nucleus integrates the central influences of testosterone on the paraventricular nucleus of the hypothalamus and its extended circuitries.	2010-09-01	20810896
Cell viability and PSA secretion assays in LNCaP cells: a tiered in vitro approach to screen chemicals with a prostate-mediated effect on male reproduction within the ReProTect project.	2010-08	20363314
Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells.	2009-08	19672399
Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism.	2008-04	18324785
1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) disrupts the estrogen-androgen balance regulating the growth of hormone-dependent breast cancer cells.	2008	18275596
Ligand-specific dynamics of the androgen receptor at its response element in living cells.	2007-03	17189428
Regulation of A Disintegrin And Metalloproteinase with ThromboSpondin repeats-1 expression in human endometrial stromal cells by gonadal steroids involves progestins, androgens, and estrogens.	2006-12	17018655
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006-11	16497524
Synthesis and biological evaluation of a nonsteroidal bromine-76-labeled androgen receptor ligand 3-[76Br]bromo-hydroxyflutamide.	2006-08	16934689
The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions.	2005-07-12	15994236
Evidence that inhibited prostatic epithelial bud formation in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed C57BL/6J fetal mice is not due to interruption of androgen signaling in the urogenital sinus.	2004-06	15056816
Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay.	2004-02	15084347
Androgen dependent regulation of bacillus Calmette-Guerin induced interleukin-6 expression in human transitional carcinoma cell lines.	2003-11	14532843
UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay.	2003-07	12730620
Acquisition of agonistic properties of nonsteroidal antiandrogens after treatment with oncostatin M in prostate cancer cells.	2002-07	12114440
Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening.	2002-03	11861975
A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists.	2002-03	11861974
Role of cadmium in the regulation of AR gene expression and activity.	2002-01	11751618
Regulation of GCDFP-15 expression in human mammary cancer cells.	1999-08	10402478
Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals.	1999-03-01	10053169
Androgen antagonistic effect of estramustine phosphate (EMP) metabolites on wild-type and mutated androgen receptor.	1998-05-01	10076535

Patents

Sample Use Guides

In Vivo Use Guide

Single injection in one lobe of 2-8 mL ready-made paste (corresponding to 400-1600 mg 2-Hydroxyflutamid)

Route of Administration: Other

In Vitro Use Guide

The dihydrotestosterone-mediated induction of Amyloid precursor protein (APP) mRNA expression was potently suppressed by 10 uM of an androgen receptor blocker hydroxyflutamide (0.35-fold and P<0.01, compared to a group treated by DHT alone), whereas hydroxyflutamide alone did not significantly alter APP mRNA level in MCF-7cells (0.79-fold, P=0.69).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:37:19 GMT 2025` Edited by `admin` on `Mon Mar 31 20:37:19 GMT 2025`
Record UNII	31D90UKP5Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HYDROXYFLUTAMIDE

Common Name

English

.ALPHA.-HYDROXYFLUTAMIDE

Preferred Name

English

2-HYDROXY-2-METHYL-N-(4-NITRO-3-(TRIFLUOROMETHYL)PHENYL)PROPANAMIDE

Systematic Name

English

3-(TRIFLUOROMETHOXY)BENZONITRILE

Systematic Name

English

PROPANAMIDE, 2-HYDROXY-2-METHYL-N-(4-NITRO-3-(TRIFLUOROMETHYL)PHENYL)-

Systematic Name

English

2-HYDROXYFLUTAMIDE

Common Name

English

HYDROXY-FLUTAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C146993