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 8146		0.9 µM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: http://www.drugbank.ca/drugs/DB00499	Antagonist 2737		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 8307	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 1670			inhibitor 1570 inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A8 36 UGT1A10 32 OATP2B1 121 CYP1B1 19	CYP1B1 90 CYP1A1 344 CYP1A2 1013 CYP2C19 955 CYP3A5 383 MRP1 102	P-gp 252

Drug as perpetrator

Target	Modality	Activity
UGT1A10 41	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
UGT1A8 48	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/25834030/	unlikely
CYP1B1 66	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes [Ki 1 uM]
BCRP 751	supressor 149 Sources: https://pubmed.ncbi.nlm.nih.gov/17823853/	yes
MATE1 304	supressor 149 Sources: https://pubmed.ncbi.nlm.nih.gov/25862351/	yes
OATP2B1 124	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
P-gp 1588	activator 208 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 1588	inducer 1515 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 344	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/ \| https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP1B1 90	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/11160641/	yes
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/ \| https://pubmed.ncbi.nlm.nih.gov/9351907/	yes
CYP3A5 383	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17403914/	yes
MRP1 102	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12750271/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inducer 27 Sources: https://pubmed.ncbi.nlm.nih.gov/18599551/
hERG 1603	inhibitor 1584 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
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
[What is the role of hormonal treatments in acne?].	2001 Apr	11450396
[Clinical efficacy of treatment with low-dose flutamide in maximum androgen blockade therapy].	2001 Apr	11411099
[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
[Hirsutism, flutamide and hepatotoxicity].	2001 Apr	11333662
Appropriate column configurations for the rapid analysis and semipreparative purification of the radiolabeled drug flutamide by high-performance liquid chromatography.	2001 Apr 20	11358217
Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells.	2001 Apr 27	11322786
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
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
Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects.	2001 Aug	11458055
Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues.	2001 Aug	11452136
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
Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture.	2001 Feb-May	11428707
M1 prostate cancer with a serum level of prostate-specific antigen less than 10 ng/mL.	2001 Jul	11442659
Testosterone inhibits spermatogonial differentiation in juvenile spermatogonial depletion mice.	2001 Jul	11415997
The subnuclear three-dimensional image analysis of androgen receptor fused to green fluorescence protein.	2001 Jul 27	11369770
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
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
Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.	2001 Jun 10	11403897
Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences.	2001 Jun 15	11391684
[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
Testosterone receptor blockade restores cellular immunity in male mice after burn injury.	2001 May	11312147
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
Initial induction and subsequent reduction of alpha(2u)-globulin in urine and serum of mature male rats after repeated intraperitoneal injections of (anti)estrogen.	2001 May 11	11337107
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
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
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

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