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 8297		0.9 µM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: http://www.drugbank.ca/drugs/DB00499	Antagonist 2778		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 8429	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 1989

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 1737			inhibitor 1612 inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A8 36 UGT1A10 32 OATP2B1 123 CYP1B1 19	CYP1B1 92 CYP1A1 349 CYP1A2 1054 CYP2C19 991 CYP3A5 395 MRP1 107	P-gp 257

Drug as perpetrator

Target	Modality	Activity
UGT1A10 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
UGT1A8 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
CYP1B1 67	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes [Ki 1 uM]
BCRP 773	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/17823853/	yes
MATE1 308	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/25862351/	yes
OATP2B1 126	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
P-gp 1650	activator 214 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 1650	inducer 1573 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 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP1A2 1054	substrate 3367 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 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
MRP1 107	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12750271/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inducer 27 Sources: https://pubmed.ncbi.nlm.nih.gov/18599551/
hERG 1647	inhibitor 1626 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
[Risk factor of liver disorders caused by flutamide--statistical analysis using multivariate logistic regression analysis].	1999 Aug	10500955
[Fatal hepatic failure following hepatitis caused by flutamide: a case report].	1999 May	10386060
Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism.	2000 Dec	11228061
[Fulminant liver failure induced by flutamide].	2000 Jun	10985104
Ultrastructural and quantitative immunohistochemical changes induced by nonsteroid antiandrogens on pituitary gonadotroph population of prepubertal male rats.	2001	11340263
Optimal starting time for flutamide to prevent disease flare in prostate cancer patients treated with a gonadotropin-releasing hormone agonist.	2001	11316974
[What is the role of hormonal treatments in acne?].	2001 Apr	11450396
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
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
Hormonal regulation of appetite and body mass in patients with advanced prostate cancer treated with combined androgen blockade.	2001 Jan	11227729
Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function.	2001 Jan	11145738
Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice.	2001 Jan	11133514
Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group.	2001 Jan 1	11134196
Virilization of the urogenital sinus of the tammar wallaby is not unique to 5alpha-androstane-3alpha,17beta-diol.	2001 Jul 5	11476945
Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons.	2001 Jun	11389183
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
[Complete remission of brain metastases from prostate cancer by gamma knife radiosurgery: a case report].	2001 May	11433755
A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma.	2001 May	11341643
Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells.	2001 May	11312142
Possible androgenic/anti-androgenic activity of the insecticide fenitrothion.	2001 May-Jun	11404828
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
Replacement of surgical castration by GnRH-inhibition or Leydig cell ablation in the male rat Hershberger antiandrogen assay.	2001 Oct	11603962
Differential gene expression in response to methoxychlor and estradiol through ERalpha, ERbeta, and AR in reproductive tissues of female mice.	2001 Sep	11509743
Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive prostate cancer cells.	2001 Sep 5	11535706

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