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

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 167 Target ID: CHEMBL1871 Sources: http://en.pharmacodia.com/yaodu/html/v1/chemicals/33774f2e84b754ad8973804d0e907534.html \| https://www.ncbi.nlm.nih.gov/pubmed/3713990	Antagonist 2778		0.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Prostate cancer 178 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 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 80 inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 402 CYP19A1 60	P-gp 1537 MRP1 107

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=17388977	inconclusive [IC50 25.1189 uM]
CYP3A4 1925	activator 214 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=17388977	no [Activation 25.1189 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144213961	no [IC50 39.8045 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17409513/	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007324	no
MRP1 107	substrate 3367 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
AK Scientific	X6072	https://aksci.com/item_detail.php?cat=X6072
Aceschem	ACF022416	https://www.aceschem.com/catalog/search.do?q=ACF022416
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
Enamine	EN300-127735	https://www.enaminestore.com/catalog/EN300-127735
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
MolPort	MolPort-001-771-895	https://www.molport.com/shop/molecule-link/MolPort-001-771-895
Molcore	MC103078	http://www.molcore.com/CatMC103078.html
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
eMolecules	3717966	https://orderbb.emolecules.com/search/#?query=3717966
eNovation Chemicals	K31222	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K31222&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6726517919	https://mcule.com/MCULE-6726517919/

PubMed

Title	Date	PubMed
Regulation of GCDFP-15 expression in human mammary cancer cells.	1999 Aug	10402478
Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals.	1999 Mar 1	10053169
Role of cadmium in the regulation of AR gene expression and activity.	2002 Jan	11751618
Acquisition of agonistic properties of nonsteroidal antiandrogens after treatment with oncostatin M in prostate cancer cells.	2002 Jul	12114440
Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening.	2002 Mar	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 Mar	11861974
Ligand-specific dynamics of the androgen receptor at its response element in living cells.	2007 Mar	17189428
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
Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism.	2008 Apr	18324785
Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells.	2009 Aug	19672399
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 Aug	20363314
The medial preoptic nucleus integrates the central influences of testosterone on the paraventricular nucleus of the hypothalamus and its extended circuitries.	2010 Sep 1	20810896
Unexpected binding orientation of bulky-B-ring anti-androgens and implications for future drug targets.	2011 Jun 9	21506597
Ligand-independent androgen receptor antagonism caused by the newly developed pesticide pyrifluquinazon (PFQ).	2013 Jan	23146716
Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and Its active metabolite hydroxyflutamide using HepG2/C3a microfluidic biochips.	2013 Mar	22843567
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 Dec	26318274
Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach.	2015 Dec 15	26485406

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).

Name

Type

Language

HYDROXYFLUTAMIDE

Common 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

.ALPHA.-HYDROXYFLUTAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C146993