FLUTAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H11F3N2O3
Molecular Weight	276.2123
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C(=Nc1ccc(c(c1)C(F)(F)F)N(=O)=O)O

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

Molecular Formula	C11H11F3N2O3
Molecular Weight	276.2123
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 7728		0.9 µM [IC50]
Androgen Receptor 163 Target ID: CHEMBL1871 Sources: http://www.drugbank.ca/drugs/DB00499	Antagonist 2575		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 8043	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 1601			inhibitor 1475 inducer 22

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A8 33 UGT1A10 29 OATP2B1 109 CYP1B1 19	CYP1B1 88 CYP1A1 325 CYP1A2 972 CYP2C19 910 CYP3A5 367 MRP1 97	P-gp 248

Drug as perpetrator

Target	Modality	Activity
UGT1A10 38	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
UGT1A8 45	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
CYP1B1 63	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes [Ki 1 uM]
BCRP 713	supressor 140 Sources: https://pubmed.ncbi.nlm.nih.gov/17823853/	yes
MATE1 292	supressor 140 Sources: https://pubmed.ncbi.nlm.nih.gov/25862351/	yes
OATP2B1 112	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
P-gp 1514	activator 202 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 1514	inducer 1440 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 325	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP1A2 972	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/ \| https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP1B1 88	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP2C19 910	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP3A5 367	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
MRP1 97	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/12750271/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inducer 25 Sources: https://pubmed.ncbi.nlm.nih.gov/18599551/
hERG 1507	inhibitor 1489 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
Effects of an environmental anti-androgen on erectile function in an animal penile erection model.	2000 Apr	10737536
Examination of selected food additives and organochlorine food contaminants for androgenic activity in vitro.	2000 Feb	10696776
Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organization for Research and Treatment of Cancer.	2000 Jan	10646878
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
[Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials].	2001 Apr	11355590
Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade.	2001 Apr	11247793
The effects of intrahippocampal testosterone and flutamide on spatial localization in the Morris water maze.	2001 Apr 6	11282357
Androgen-induced up-regulation of tubulin isoforms in neuroblastoma cells.	2001 Aug	11520906
Radiation and hormonal therapy for locally advanced and clinically localized prostate cancer.	2001 Aug	11502455
Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer.	2001 Aug	11502439
Testosterone suppresses spermatogenesis in juvenile spermatogonial depletion (jsd ) mice.	2001 Aug	11466222
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
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
[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].	2001 Jan	11235226
Hormonal regulation of appetite and body mass in patients with advanced prostate cancer treated with combined androgen blockade.	2001 Jan	11227729
An electrochemical evidence of free radicals formation from flutamide and its reactivity with endo/xenobiotics of pharmacological relevance.	2001 Jan	11206916
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
Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice.	2001 Jan	11133514
Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function.	2001 Jan	11121992
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
Sexual dimorphism and aromatase in the rat retina.	2001 Jan 31	11172896
Virilization of the urogenital sinus of the tammar wallaby is not unique to 5alpha-androstane-3alpha,17beta-diol.	2001 Jul 5	11476945
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
Steroid-sensitive gene-1 is an androgen-regulated gene expressed in prostatic smooth muscle cells in vivo.	2001 Jun	11357054
Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.	2001 Jun 10	11403897
Testosterone perturbs epidermal permeability barrier homeostasis.	2001 Mar	11231319
Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs. short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy.	2001 Mar 15	11240235
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
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
Androgen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27.	2001 May	11328857
Effects of acute stanozolol treatment on puberty in female rats.	2001 May	11319152
Dissection and weighing of accessory sex glands after formalin fixation, and a 5-day assay using young mature rats are reliable and feasible in the Hershberger assay.	2001 May 11	11337110
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
Possible androgenic/anti-androgenic activity of the insecticide fenitrothion.	2001 May-Jun	11404828
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
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
Attenuation of vascular endothelial dysfunction by testosterone receptor blockade after trauma and hemorrhagic shock.	2001 Oct	11585509
Flutamide-induced acute hepatitis in advanced prostate cancer patients.	2001 Sep	11563686
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

Substance Class	Chemical Created by `admin` on `Fri Jun 25 20:55:42 UTC 2021` Edited by `admin` on `Fri Jun 25 20:55:42 UTC 2021`
Record UNII	76W6J0943E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUTAMIDE

Official Name

English

NSC-215876

Code

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

FLUTAMIDE [EP]

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