FLUTAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H11F3N2O3
Molecular Weight	276.2118
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=MKXKFYHWDHIYRV-UHFFFAOYSA-N

InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00499
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/flutamide.html

Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration. Flutamide blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen. Flutamide is used for the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
LNCaP 3 Target ID: CHEMBL612518 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21600678	Inhibitor 8228		0.9 µM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: http://www.drugbank.ca/drugs/DB00499	Antagonist 2760		102.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic carcinoma of the prostate 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18554s23lbl.pdf	Primary		Approved 8360	EULEXIN Approved Use Flutamide capsules are indicated for use in combination with LHRH agonists for the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate. Launch Date 6.01776E11

C_max

Value	Dose	Analyte	Population
53.4 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10073738	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
112.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2754024	250 mg 3 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
25.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2754024	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
96.4 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10073738	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
212.1 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2754024	250 mg 3 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
63 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2754024	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10073738	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Co-administed with:: ethinyl estradiol(0.020 mg) desogestrel(0.15 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/18339379/	unhealthy, 26.3 n = 83 Health Status: unhealthy Condition: hirsutism Age Group: 26.3 Sex: F Population Size: 83 Sources: https://pubmed.ncbi.nlm.nih.gov/18339379/	Disc. AE: Abdominal pain, Vomiting... Other AEs: Flatulence, Diarrhea... AEs leading to discontinuation/dose reduction: Abdominal pain (12 patients) Vomiting (8 patients) Headache (9 patients) Hypertransaminasemia (3 patients) Fatty liver (1 patient) Weight gain (5 patients) Other AEs: Flatulence (15 patients) Diarrhea (5 patients) Dry skin (10 patients) Nephrolithiasis (1 patient) Leg pain (2 patients) Dyslipidemia (4 patients) Fluid retention (4 patients) Epigastralgia (3 patients) Dyspepsia (2 patients) Nausea (9 patients) Vaginal infection (1 patient) Constipation (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/18339379/
250 mg 3 times / day multiple, oral Recommended Dose: 250 mg, 3 times / day Route: oral Route: multiple Dose: 250 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8977067/	unhealthy, adult n = 75 Health Status: unhealthy Condition: prostate cancer Age Group: adult Sex: M Population Size: 75 Sources: https://pubmed.ncbi.nlm.nih.gov/8977067/	Disc. AE: Diarrhea, Impaired liver function... Other AEs: Hot flushes, Breast tenderness... AEs leading to discontinuation/dose reduction: Diarrhea (severe, 1.3%) Impaired liver function (4%) Gynecomastia (1.3%) Other AEs: Hot flushes (all grades, 25%) Breast tenderness (all grades, 49%) Nausea and vomiting (all grades, 22%) Appetite lost (all grades, 17%) Diarrhea (all grades, 16%) Hot flushes (severe, 4%) Breast tenderness (severe, 7%) Nausea and vomiting (severe, 1.3%) Appetite lost (severe, 1.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/8977067/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709			inhibitor 1599 inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A8 36 UGT1A10 32 OATP2B1 122 CYP1B1 19	CYP1B1 92 CYP1A1 348 CYP1A2 1032 CYP2C19 985 CYP3A5 391 MRP1 106	P-gp 257

Drug as perpetrator

Target	Modality	Activity
UGT1A10 41	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
UGT1A8 48	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
CYP1B1 68	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes [Ki 1 uM]
BCRP 765	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/17823853/	yes
MATE1 306	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/25862351/	yes
OATP2B1 125	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
P-gp 1626	activator 210 Sources: https://pubmed.ncbi.nlm.nih.gov/20041327/ \| https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/j.clpt.2004.12.055	yes
P-gp 1626	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/20041327/ \| https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/j.clpt.2004.12.055	yes

Drug as victim

Target	Modality	Activity
CYP1A1 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/ \| https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP1B1 92	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP3A5 391	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
MRP1 106	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12750271/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inducer 27 Sources: https://pubmed.ncbi.nlm.nih.gov/18599551/
hERG 1632	inhibitor 1613 Sources: https://pubmed.ncbi.nlm.nih.gov/18953086/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5132	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5132
ChemicalBook	CB2468110	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2468110
MolPort	MolPort-001-771-894	https://www.molport.com/shop/molecule-link/MolPort-001-771-894
Selleck Chemicals	Flutamide(Eulexin)	http://www.selleckchem.com/products/Flutamide(Eulexin).html
ZINC	ZINC000003812944	http://zinc15.docking.org/substances/ZINC000003812944
eMolecules	538525	https://www.emolecules.com/cgi-bin/more?vid=538525

PubMed

Title	Date	PubMed
Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro.	2000 Feb	10696776
[Toxic hepatitis caused by flutamide and hirsutism].	2000 May	10902281
Ultrastructural and quantitative immunohistochemical changes induced by nonsteroid antiandrogens on pituitary gonadotroph population of prepubertal male rats.	2001	11340263
A risk-benefit assessment of pharmacological therapies for hirsutism.	2001	11330656
Treatment of localized prostate cancer with intermittent triple androgen blockade: preliminary results in 110 consecutive patients.	2001	11306729
[What is the role of hormonal treatments in acne?].	2001 Apr	11450396
[Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials].	2001 Apr	11355590
Feasibility and potential gains of enhancing the subacute rat study protocol (OECD test guideline no. 407) by additional parameters selected to determine endocrine modulation. A pre-validation study to determine endocrine-mediated effects of the antiandrogenic drug flutamide.	2001 Apr	11354908
Chemoprevention for prostatic carcinoma: The role of flutamide in patients with prostatic intraepithelial neoplasia.	2001 Apr	11295624
Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade.	2001 Apr	11247793
Appropriate column configurations for the rapid analysis and semipreparative purification of the radiolabeled drug flutamide by high-performance liquid chromatography.	2001 Apr 20	11358217
Regulation of keratinocyte growth factor receptor and androgen receptor in epithelial cells of the human prostate.	2001 Aug	11458116
Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate.	2001 Aug	11458057
Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.	2001 Aug 1	11483335
Determination of 2-hydroxyflutamide in human plasma by high-performance liquid chromatography and its application to pharmacokinetic studies.	2001 Aug 5	11499624
[Anemia and neoadjuvant hormone therapy in radical surgery of localized cancer of the prostate].	2001 Feb	11345792
Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor.	2001 Feb 23	11226426
Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism.	2001 Feb 23	11172772
Association of African-American ethnic background with survival in men with metastatic prostate cancer.	2001 Feb 7	11158191
[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].	2001 Jan	11235226
An electrochemical evidence of free radicals formation from flutamide and its reactivity with endo/xenobiotics of pharmacological relevance.	2001 Jan	11206916
The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways.	2001 Jan	11202367
Lack of methemoglobinemia with flutamide.	2001 Jan	11197580
Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function.	2001 Jan	11145738
Sexual dimorphism and aromatase in the rat retina.	2001 Jan 31	11172896
The subnuclear three-dimensional image analysis of androgen receptor fused to green fluorescence protein.	2001 Jul 27	11369770
Kap promoter analysis in vivo: a regulatory role for a truncated L1 repeat.	2001 Jul 5	11476941
Strain sensitivity differences in the Hershberger assay.	2001 Jul-Aug	11489600
Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons.	2001 Jun	11389183
Sex differences in infant rhesus macaque separation-rejection vocalizations and effects of prenatal androgens.	2001 Jun	11374912
Developmental and hormonal regulation of type II DNA topoisomerase in rat testis.	2001 Jun	11357056
Steroid-sensitive gene-1 is an androgen-regulated gene expressed in prostatic smooth muscle cells in vivo.	2001 Jun	11357054
Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences.	2001 Jun 15	11391684
The biological effect of phthalate esters on transabdominal migration of the testis in fetal rats in comparison with the antiandrogen flutamide.	2001 Mar	11315278
Administration of tamoxifen but not flutamide to hormonally intact, adult male rats mimics the effects of short-term gonadectomy on the catecholamine innervation of the cerebral cortex.	2001 Mar 19	11223814
[Adenocarcinoma of prostate in men younger than 50--rectal palpation mandatory with micturition problems].	2001 Mar 24	11293992
Suppression of androgen action and the induction of gross abnormalities of the reproductive tract in male rats treated neonatally with diethylstilbestrol.	2001 Mar-Apr	11229807
A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma.	2001 May	11341643
Effects of acute stanozolol treatment on puberty in female rats.	2001 May	11319152
Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells.	2001 May	11312142
Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia.	2001 May	11287329
Chemical andropause and amyloid-beta peptide.	2001 May 2	11325319
Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands.	2001 May 24	11356108
Quantification of antiandrogen effect determined by Lightcycler technology.	2001 May 28	11376863
Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man.	2001 May-Jun	11392370
Actions of the endocrine disruptor methoxychlor and its estrogenic metabolite on in vitro embryonic rat seminiferous cord formation and perinatal testis growth.	2001 May-Jun	11390175
Tamoxifen is an acute, estrogen-like, coronary vasodilator of porcine coronary arteries in vitro.	2001 Nov	11602812
Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--a preliminary report.	2001 Nov 1	11597799
Replacement of surgical castration by GnRH-inhibition or Leydig cell ablation in the male rat Hershberger antiandrogen assay.	2001 Oct	11603962
Flutamide-induced acute hepatitis in advanced prostate cancer patients.	2001 Sep	11563686

Patents

Sample Use Guides

In Vivo Use Guide

For use in locally confined stage B2-C and stage D2 metastatic carcinoma of the prostate: 250 mg orally every 8 hours.

Route of Administration: Oral

In Vitro Use Guide

Flutamide inhibited spiggin production in vitro at a concentration as low as 10(-12) M in cultures of primed female stickleback kidney cells

Name

Type

Language

FLUTAMIDE

Official Name

English

NSC-215876

Code

English

FLUTAMIDE [EP IMPURITY]

Common Name

English

FLUTAMIDE [EP MONOGRAPH]

Common Name

English

FLUTAMIDE [USAN]

Common Name

English

EULEXIN

Brand Name

English

FLUTAMIDE [MART.]

Common Name

English

FLUTAMIDE [ORANGE BOOK]

Common Name

English

SCH-13521

Code

English

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

Systematic Name

English

SCH 13521

Code

English

.ALPHA.,.ALPHA.,.ALPHA.-TRIFLUORO-2-METHYL-4'-NITRO-M-PROPIONOTOLUIDIDE

Common Name

English

FLUTAMIDE [USP-RS]

Common Name

English

FLUTAMIDE [MI]

Common Name

English

Flutamide [WHO-DD]

Common Name

English

FLUTAMIDE [USP MONOGRAPH]

Common Name

English

FLUTAMIDE [JAN]

Common Name

English

flutamide [INN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175560