NILUTAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H10F3N3O4
Molecular Weight	317.2212
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)C(=O)N(c2ccc(c(c2)C(F)(F)F)N(=O)=O)C(=N1)O

InChI

InChIKey=XWXYUMMDTVBTOU-UHFFFAOYSA-N

InChI=1S/C12H10F3N3O4/c1-11(2)9(19)17(10(20)16-11)6-3-4-8(18(21)22)7(5-6)12(13,14)15/h3-5H,1-2H3,(H,16,20)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00665
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf

Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide. Nilutamide competes with androgen for the binding of androgen receptors, consequently blocking the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. This blockade of androgen receptors may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. Nilutamide is used in combination with surgical castration for the treatment of metastatic prostate cancer involving distant lymph nodes, bone, or visceral organs (Stage D2). Nilutamide is sold under the brand names Nilandron (US), Anandron (CA)).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 163 Target ID: CHEMBL1871 Sources: http://www.drugbank.ca/drugs/DB00665	Antagonist 2575		9.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic prostate cancer 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf	Primary		Approved 8043	NILANDRON Approved Use Metastatic Prostate Cancer Nilutamide Tablets are indicated for use in combination with surgical castration for the treatment of metastatic prostate cancer (Stage D2). Launch Date 8.4300477E11

C_max

Value	Dose	Co-administered	Analyte	Population
2.3 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8453188	0.3 g single, oral dose: 0.3 g route of administration: Oral experiment type: SINGLE co-administered:		NILUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.3 mg/L DRUG LABEL https://gp2u.com.au/static/pdf/A/ANANDRON-PI.pdf	0.3 g single, oral dose: 0.3 g route of administration: Oral experiment type: SINGLE co-administered:		NILUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
84 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8453188	0.3 g single, oral dose: 0.3 g route of administration: Oral experiment type: SINGLE co-administered:		NILUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
49 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8453188	0.3 g single, oral dose: 0.3 g route of administration: Oral experiment type: SINGLE co-administered:		NILUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
56 h DRUG LABEL https://gp2u.com.au/static/pdf/A/ANANDRON-PI.pdf	0.3 g single, oral dose: 0.3 g route of administration: Oral experiment type: SINGLE co-administered:		NILUTAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2203517 Page: p.1075	unhealthy, 47-93 n = 53 Health Status: unhealthy Condition: Metastatic prostate cancer Age Group: 47-93 Sex: M Population Size: 53 Sources: https://pubmed.ncbi.nlm.nih.gov/2203517 Page: p.1075	DLT: Nausea, Vomiting... Disc. AE: Hot flashes, Interstitial lung disease... Dose limiting toxicities: Nausea (7.5%) Vomiting (7.5%) AEs leading to discontinuation/dose reduction: Hot flashes (5.7%) Interstitial lung disease (3.8%) Visual disturbance NOS (1.9%) Pruritus (1.9%) Dizziness (1.9%) Headache (1.9%) Hepatic enzyme increased (1.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/2203517 Page: p.1075
13 g single, oral Overdose Dose: 13 g Route: oral Route: single Dose: 13 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141	unhealthy, 79 n = 1 Health Status: unhealthy Condition: Metastatic prostate cancer Age Group: 79 Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141	Disc. AE: Vomiting, Diarrhoea... AEs leading to discontinuation/dose reduction: Vomiting (moderate) Diarrhoea (moderate) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141
900 mg 1 times / day multiple, oral Highest studied dose Dose: 900 mg, 1 times / day Route: oral Route: multiple Dose: 900 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141	unhealthy n = 4 Health Status: unhealthy Condition: Metastatic prostate cancer Sex: M Population Size: 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141	Disc. AE: Gastrointestinal disorders, Nausea... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders Nausea Vomiting Malaise Headache Dizziness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf https://pubmed.ncbi.nlm.nih.gov/2810141
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Co-administed with:: leuprolide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.8	unhealthy n = 209 Health Status: unhealthy Condition: Metastatic prostate cancer Sex: M Population Size: 209 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.8	Disc. AE: Visual disturbances... AEs leading to discontinuation/dose reduction: Visual disturbances (1 - 2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.8
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Metastatic prostate cancer Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.3	Disc. AE: Interstitial pneumonitis, Pulmonary fibrosis... AEs leading to discontinuation/dose reduction: Interstitial pneumonitis (2%) Pulmonary fibrosis (grade 5, rare) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.3
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Metastatic prostate cancer Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.4	Disc. AE: Liver injury... AEs leading to discontinuation/dose reduction: Liver injury (severe, rare) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207631Orig1s000lbl.pdf Page: p.4

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7573	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7573
ChemicalBook	CB3278091	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3278091
MolPort	MolPort-003-666-533	https://www.molport.com/shop/molecule-link/MolPort-003-666-533
MolPort	MolPort-005-975-300	https://www.molport.com/shop/molecule-link/MolPort-005-975-300
ZINC	ZINC000003874498	http://zinc15.docking.org/substances/ZINC000003874498
eMolecules	592881	https://www.emolecules.com/cgi-bin/more?vid=592881

PubMed

Title	Date	PubMed
Flare Associated with LHRH-Agonist Therapy.	2001	16986003
Androgen deprivation and other treatments for advanced prostate cancer.	2001	16986000
Therapeutic androgen receptor ligands.	2003	16604181
Major impact of hormonal therapy in localized prostate cancer--death can already be an exception.	2004 Dec	15698538
Steroid activities comparison of natural and food wrap compounds in human breast cancer cell lines.	2004 Jun	15110097
Vaccine therapy for a patient with androgen-insensitive prostate cancer without evidence of measurable disease on scans.	2004 May-Jun	15133542
Monotherapy in advanced prostate cancer: an overview.	2004 Sep	15494685
Intermittent androgen deprivation for biologic recurrence after radical prostatectomy: long-term experience.	2005 Apr	15833516
Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer.	2005 Aug	16006888
How are hemoglobin levels affected by androgen deprivation in non-metastatic prostate cancer patients?	2005 Feb	15777493
Three-dimensional structure-activity relationships of nonsteroidal ligands in complex with androgen receptor ligand-binding domain.	2005 Feb 24	15715462
[From the finger to the eye!...].	2005 Jul	16129183
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Combined androgen blockade: the case for bicalutamide.	2005 Mar	15882477
Prolonged response to nilutamide in a patient with stage D0.5 prostate cancer who previously failed androgen deprivation therapy.	2005 Mar-Apr	15767834
Prostate cancer PET bioprobes: synthesis of [18F]-radiolabeled hydroxyflutamide derivatives.	2005 Nov 15	16054371
Efficacy of nilutamide as secondary hormonal therapy in androgen-independent prostate cancer.	2005 Oct	16153200
Mitochondrial permeability transition as a source of superoxide anion induced by the nitroaromatic drug nimesulide in vitro.	2005 Oct 1	16140214
Nontranscriptional regulation of cardiac repolarization currents by testosterone.	2005 Sep 20	16157773
Androgenic and antiandrogenic effects and expression of androgen receptor in mouse embryonic stem cells.	2006 Apr	16616092
Androgen receptor is responsible for rat organic cation transporter 2 gene regulation but not for rOCT1 and rOCT3.	2006 Apr	16550473
The role of steroids in follicular growth.	2006 Apr 10	16603089
Antiandrogen treatments in locally advanced prostate cancer: are they all the same?	2006 Aug	16845534
Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones.	2006 Dec	16985185
Metabolism of nilutamide in rat lung.	2006 Jan 12	16313887
GREB1 is a novel androgen-regulated gene required for prostate cancer growth.	2006 Jun 1	16496412
Recent progress in hormonal therapy for advanced prostate cancer.	2006 May	16679855
Combined androgen blockade: an update.	2006 May	16631454
Bioactivation and hepatotoxicity of nitroaromatic drugs.	2006 Oct	17073576
[Keyrole of endocrinology in the victory against prostate cancer].	2006 Sep	16980238
Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.	2007 Feb 16	17196933
New therapeutic targets in the treatment of prostate cancer.	2007 Jan	19675766
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay.	2007 Jan	16857237
Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism.	2008 Apr	18324785
The androgen receptor can signal through Wnt/beta-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens.	2008 Jan 24	18218096
Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy.	2008 Jul 15	18628467
Delayed dark adaptation caused by nilutamide.	2008 Jun	18562852
Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide.	2008 Mar 27	18303829
A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.	2008 Nov 5	18986533
FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects.	2008 Sep 24	18816385
Fulminant hepatic failure due to nilutamide hepatotoxicity.	2009 Apr	18688719
Fasting and cancer treatment in humans: A case series report.	2009 Dec 31	20157582
CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer.	2009 Mar 10	19223900
Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway.	2010 Apr	20194727
The evolutionary impact of androgen levels on prostate cancer in a multi-scale mathematical model.	2010 Apr 20	20406442
A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899.	2010 Feb 24	20178647
Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor.	2010 Jan 26	20102617
Involvement of androgen receptor in nitric oxide production induced by icariin in human umbilical vein endothelial cells.	2010 Jun 3	20416296
Activity of antiandrogens against juvenile and adult Schistosoma mansoni in mice.	2010 Sep	20576641

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is 300 mg once a day for 30 days, followed thereafter by 150 mg once a day. Nilutamide Tablets can be taken with or without food.

Route of Administration: Oral

In Vitro Use Guide

At concentrations expected in the human liver (110 uM), nilutamide inhibited hexobarbital hydroxylase, benzphetamine N-demethylase, benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase activities by 85, 40, 35 and 25%, respectively in human liver microsomes.

Name

Type

Language

NILUTAMIDE

Official Name

English

NILUTAMIDE [INN]

Common Name

English

NILUTAMIDE [ORANGE BOOK]

Common Name

English

5,5-DIMETHYL-3-(.ALPHA.,.ALPHA.,.ALPHA.-TRIFLUORO-4-NITRO-M-TOLYL)HYDANTOIN

Systematic Name

English

2,4-IMIDAZOLIDINEDIONE, 5,5-DIMETHYL-3-(4-NITRO-3-(TRIFLUOROMETHYL)PHENYL)-

Systematic Name

English

NILUTAMIDE [EP MONOGRAPH]

Common Name

English

NILUTAMIDE [USP MONOGRAPH]

Common Name

English

NILUTAMIDE [MI]

Common Name

English

RU 23908

Code

English

NILUTAMIDE [MART.]

Common Name

English

NSC-758683

Code

English

NILUTAMIDE [VANDF]

Common Name

English

RU-23908

Code

English

NILUTAMIDE [USP-RS]

Common Name

English

NILANDRON

Brand Name

English

NILUTAMIDE [USAN]

Common Name

English

NILUTAMIDE [WHO-DD]

Common Name

English

Classification Tree Code System Code

LIVERTOX

686