ENZALUTAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H16F4N4O2S
Molecular Weight	464.436
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CNC(=O)C1=CC=C(C=C1F)N2C(=S)N(C(=O)C2(C)C)C3=CC(=C(C=C3)C#N)C(F)(F)F

InChI

InChIKey=WXCXUHSOUPDCQV-UHFFFAOYSA-N

InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)

HIDE SMILES / InChI

Molecular Formula	C21H16F4N4O2S
Molecular Weight	464.436
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Enzalutamide (brand name Xtandi) is an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. It was developed at UCLA and marketed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer. Through a mechanism that is reported to be different from other approved AR antagonists, enzalutamide inhibits the activity of prostate cancer cell ARs, which may result in a reduction in prostate cancer cell proliferation and, correspondingly, a reduction in the serum prostate specific antigen (PSA) level. AR over-expression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 167	Inhibitor 8,297		21.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Castrate-resistant prostate cancer 20	Primary		Approved 8,429	XTANDI

C_max

Value	Dose	Co-administered	Analyte	Population
3.4 μg/mL	150 mg single, oral		ENZALUTAMIDE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
340 μg × h/mL	150 mg single, oral		ENZALUTAMIDE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
6 day	150 mg single, oral		ENZALUTAMIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.94%	150 mg single, oral		ENZALUTAMIDE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3	DLT: Rash...
300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3	DLT: Seizure...
300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3	Other AEs: Convulsions...
240 mg 1 times / day multiple, oral MTD	unhealthy, 68 years (range: 44–93 years ) n = 29	Disc. AE: Fatigue... Other AEs: Fatigue...
240 mg 2 times / day multiple, oral	unhealthy, 68 years (range: 44–93 years ) n = 22	DLT: Seizure...
360 mg 1 times / day multiple, oral	unhealthy, 68 years (range: 44–93 years ) n = 28	DLT: Seizure...
160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800	Disc. AE: Seizure, Infection... Other AEs: Asthenia, Asthenia...
160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800	Disc. AE: Thrombocytopenia, Colonic obstruction...

AEs

AE	Significance	Dose	Population
Rash	33% DLT, Disc. AE	300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3
Seizure	33% DLT, Disc. AE	300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3
Convulsions	grade 3-4, 33%	300 mg 2 times / day multiple, oral Highest studied dose	unhealthy, 68 years (range: 44–93 years ) n = 3
Fatigue	3% Disc. AE	240 mg 1 times / day multiple, oral MTD	unhealthy, 68 years (range: 44–93 years ) n = 29
Fatigue	grade 3-4, 17%	240 mg 1 times / day multiple, oral MTD	unhealthy, 68 years (range: 44–93 years ) n = 29
Seizure	5% DLT, Disc. AE	240 mg 2 times / day multiple, oral	unhealthy, 68 years (range: 44–93 years ) n = 22
Seizure	4% DLT, Disc. AE	360 mg 1 times / day multiple, oral	unhealthy, 68 years (range: 44–93 years ) n = 28
Seizure	0.9% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Laryngitis	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Nasopharyngitis	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Pharyngitis	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Rhinitis	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Sinusitis	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Upper respiratory tract infection	grade 1-4, 10.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Headache	grade 1-4, 12.1%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Musculoskeletal pain	grade 1-4, 15%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Neutropenia	grade 1-4, 15%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Peripheral edema	grade 1-4, 15.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Musculoskeletal stiffness	grade 1-4, 2.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hot flush	grade 1-4, 20.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Arthralgia	grade 1-4, 20.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Diarrhea	grade 1-4, 21.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Back pain	grade 1-4, 26.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Bilirubin increased	grade 1-4, 3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Epistaxis	grade 1-4, 3.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Dry skin	grade 1-4, 3.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Pruritus	grade 1-4, 3.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hypoesthesia	grade 1-4, 4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Amnesia	grade 1-4, 4.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Cognitive disorder	grade 1-4, 4.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Disturbance in attention	grade 1-4, 4.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Memory impairment	grade 1-4, 4.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Fall	grade 1-4, 4.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Pollakiuria	grade 1-4, 4.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Asthenia	grade 1-4, 50.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Fatigue	grade 1-4, 50.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hypertension	grade 1-4, 6.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Anxiety	grade 1-4, 6.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Paresthesia	grade 1-4, 6.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hematuria	grade 1-4, 6.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Cauda equina syndrome	grade 1-4, 7.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Bronchitis	grade 1-4, 8.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Lower respiratory tract infection	grade 1-4, 8.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Lung infection	grade 1-4, 8.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Pneumonia	grade 1-4, 8.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Insomnia	grade 1-4, 8.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Dizziness	grade 1-4, 9.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Vertigo	grade 1-4, 9.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Muscular weakness	grade 1-4, 9.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Epistaxis	grade 3-4, 0.1%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Amnesia	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Anxiety	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Cognitive disorder	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Disturbance in attention	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Fall	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hypoesthesia	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Memory impairment	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Musculoskeletal stiffness	grade 3-4, 0.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Dizziness	grade 3-4, 0.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Vertigo	grade 3-4, 0.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Headache	grade 3-4, 0.9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Peripheral edema	grade 3-4, 1%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Diarrhea	grade 3-4, 1.1%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Musculoskeletal pain	grade 3-4, 1.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Muscular weakness	grade 3-4, 1.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hematuria	grade 3-4, 1.8%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Hypertension	grade 3-4, 2.1%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Bronchitis	grade 3-4, 2.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Lower respiratory tract infection	grade 3-4, 2.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Lung infection	grade 3-4, 2.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Pneumonia	grade 3-4, 2.4%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Arthralgia	grade 3-4, 2.5%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Back pain	grade 3-4, 5.3%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Cauda equina syndrome	grade 3-4, 6.6%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Asthenia	grade 3-4, 9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Fatigue	grade 3-4, 9%	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Infection	grade 5, 1% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Sepsis	grade 5, 1% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Colonic obstruction	0.2% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Diarrhea	0.2% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Rash	0.2% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Thrombocytopenia	0.2% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800
Fatigue	0.6% Disc. AE	160 mg 1 times / day steady, oral Recommended	unhealthy, 69 years (range: 41-92 years) n = 800

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inducer 781	inhibitor 1,767 inducer 389 substrate 1,037	inhibitor 1,852 substrate 1,217	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C8 911 CYP2C19 1,478 CYP3A4/5 278 CYP1A2 1,524 P-gp 1,461	CYP2C8 693 P-gp 1,537 CYP3A5 395 CYP1A1 349 CYP1A2 1,054 CYP2A6 543 CYP2B6 664 CYP2C18 138 CYP2C19 991 CYP2E1 667	CYP2C19 293 CYP2C8 168

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 1,553	inducer 1,573	moderate
CYP2C9 1,819	inducer 1,573	moderate
CYP3A4 1,925	inducer 1,573	strong	yes (co-administration study)
P-gp 1,650	inhibitor 3,277	yes [IC50 1.67 uM]
CYP2C8 965	inhibitor 3,277	yes [IC50 10 uM]	no (co-administration study)
CYP2C19 1,553	inhibitor 3,277	yes [IC50 23 uM]
CYP2B6 1,001	inhibitor 3,277	yes [IC50 42 uM]
CYP2C9 1,819	inhibitor 3,277	yes [IC50 50 uM]
CYP1A2 1,692	inhibitor 3,277	yes [IC50 56 uM]
CYP2D6 1,891	inhibitor 3,277	yes
CYP3A4/5 335	inhibitor 3,277	yes
CYP2C8 965	inducer 1,573	yes	yes (co-administration study)

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A1 349	substrate 3,367	no
CYP1A2 1,054	substrate 3,367	no
CYP2A6 543	substrate 3,367	no
CYP2B6 664	substrate 3,367	no
CYP2C18 138	substrate 3,367	no
CYP2C19 991	substrate 3,367	no
CYP2C9 1,037	substrate 3,367	no
CYP2D6 1,217	substrate 3,367	no
CYP2E1 667	substrate 3,367	no
P-gp 1,537	substrate 3,367	no
CYP2C8 693	substrate 3,367	yes	N-desmethyl enzalutamide 1
CYP3A5 395	substrate 3,367	yes
CYP2C8 693	substrate 3,367	yes		yes (co-administration study)
CYP3A4 1,737	substrate 3,367	yes		yes (co-administration study)

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Sourcing

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68534	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68534
ChemicalBook	CB62500946	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62500946
MolPort	MolPort-009-679-470	https://www.molport.com/shop/molecule-link/MolPort-009-679-470
Selleck Chemicals	MDV3100	http://www.selleckchem.com/products/MDV3100.html
ZINC	ZINC000034806477	http://zinc15.docking.org/substances/ZINC000034806477
eMolecules	32176540	https://www.emolecules.com/cgi-bin/more?vid=32176540

PubMed

Title	Date	PubMed
Development of a second-generation antiandrogen for treatment of advanced prostate cancer.	2009 May 8	19359544
Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists.	2011 Nov 10	21936524
Inhibitors of androgen receptor activation function-2 (AF2) site identified through virtual screening.	2011 Sep 22	21846139
Molecular alterations and emerging targets in castration resistant prostate cancer.	2014 Mar	24418724

Patents

Sample Use Guides

In Vivo Use Guide

160 mg (four 40 mg capsules) administered orally once daily

Route of Administration: Oral

In Vitro Use Guide

Resistant cells were maintained in vitro under constant exposure to 10 μM of enzalutamide.

Substance Class	Chemical
Record UNII	93T0T9GKNU
Record Status	`Validated (UNII)`
Record Version

Name

Type

Language

ENZALUTAMIDE

Official Name

English

ENZALUTAMIDE [USAN]

Common Name

English

4-(3-(4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-4-OXO-2-THIOXOIMIDAZOLIDIN-1-YL)-2-FLUORO-N-METHYLBENZAMIDE

Systematic Name

English

Enzalutamide [WHO-DD]

Common Name

English

ENZALUTAMIDE [JAN]

Common Name

English

XTANDI

Brand Name

English

MDV 3100

Common Name

English

MDV-3100

Code

English

enzalutamide [INN]

Common Name

English

MDV3100

Code

English

ENZALUTAMIDE [VANDF]

Common Name

English

ENZALUTAMIDE [MI]

Common Name

English

BENZAMIDE, 4-(3-(4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-4-OXO-2-THIOXO-1-IMIDAZOLIDINYL)-2-FLUORO-N-METHYL-

Systematic Name

English

ENZALUTAMIDE [ORANGE BOOK]

Common Name

English

Classification Tree

Code System

Code

Anti-Androgen

NCI_THESAURUS

C146993

Established Pharmacologic Class

NDF-RT

N0000175560

Prostate cancer

LIVERTOX

NBK548070

Anti-androgens

WHO-ATC

L02BB04

Code System

Code

Type

Description

IUPHAR

6812

PRIMARY

PUBCHEM

15951529

PRIMARY

WIKIPEDIA

Enzalutamide

PRIMARY

EPA CompTox

DTXSID10912307

PRIMARY

FDA UNII

93T0T9GKNU

PRIMARY

SMS_ID

100000138095

PRIMARY

DAILYMED

93T0T9GKNU

PRIMARY

NDF-RT

N0000185507

PRIMARY

Cytochrome P450 2C9 Inducers [MoA]

ChEMBL

CHEMBL1082407

PRIMARY

DRUG BANK

DB08899

PRIMARY

INN

9621

PRIMARY

USAN

WW-149

PRIMARY

DRUG CENTRAL

4628

PRIMARY

CHEBI

68534

PRIMARY

MESH

C540278

PRIMARY

EVMPD

SUB77412

PRIMARY

CAS

915087-33-1

PRIMARY

RXCUI

1307298

PRIMARY

RxNorm

NDF-RT

N0000185607

PRIMARY

Cytochrome P450 2C19 Inducers [MoA]

NDF-RT

N0000185506

PRIMARY

Cytochrome P450 3A4 Inducers [MoA]

NCI_THESAURUS

C71744

PRIMARY

MERCK INDEX

m11683

PRIMARY

Related Record Type Details


					081I12ZA58

CYTOCHROME P450 2C19

METABOLIC ENZYME -> INDUCER

Comments:

Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.

Interaction Type:

MODERATE


					2IA57U2YZZ

ANDROGEN RECEPTOR F876L

TARGET -> INHIBITOR RESISTANT


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> INHIBITOR


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> INHIBITOR


					3OKI556HC2

DEUTENZALUTAMIDE

LABELED -> NON-LABELED

Amount:


					805SU96HKF

CYTOCHROME P450 3A5

METABOLIC ENZYME -> INHIBITOR


					EJC4C3UYXH

ANDROGEN RECEPTOR

TARGET -> AGONIST

Interaction Type:

BINDING


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Comments:

In vivo, the sum of enzalutamide and M2 exposure was increased by 2.2-fold and 1.3-fold when it was co-administered with gemfibrozil (strong CYP2C8 inhibitor) or itraconazole (strong CYP3A4 inhibitor), respectively.


					081I12ZA58

CYTOCHROME P450 2C19

METABOLIC ENZYME -> INHIBITOR


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

[97 to 98] % (average)


					0UY97CSG1T

CYTOCHROME P450 2B6

METABOLIC ENZYME -> INHIBITOR


					8E4LAA4357

CYTOCHROME P450 2D6

METABOLIC ENZYME -> INHIBITOR


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> INHIBITOR


					L0423Z5LDW

CYTOCHROME P450 2C8

METABOLIC ENZYME -> SUBSTRATE

Comments:

In vivo, the sum of enzalutamide and M2 exposure was increased by 2.2-fold and 1.3-fold when it was co-administered with gemfibrozil (strong CYP2C8 inhibitor) or itraconazole (strong CYP3A4 inhibitor), respectively. If the co-administration of enzalutamide with a strong CYP2C8 inhibitor cannot be avoided, the daily enzalutamide dose should be reduced to 80 mg.


					VK4SQL11C0

CYTOCHROME P450 1A2

METABOLIC ENZYME -> INHIBITOR

Interaction Type:

TIME-DEPENDENT INHIBITION


					2IA57U2YZZ

ANDROGEN RECEPTOR F876L

TARGET -> AGONIST


					EJC4C3UYXH

ANDROGEN RECEPTOR

TARGET -> INHIBITOR


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> INDUCER

Comments:

Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.

Interaction Type:

MODERATE


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> INDUCER

Comments:

Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided

Interaction Type:

STRONG


					L0423Z5LDW

CYTOCHROME P450 2C8

METABOLIC ENZYME -> INHIBITOR

Related Record Type Details


					5MK9M4BF22

4-(3-(4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-2,4-DIOXO-1-IMIDAZOLIDINYL)-2-FLUOROBENZOIC ACID

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:


					YF8MAL2HDY

ENZALUTAMIDE CARBOXYLIC ACID

METABOLITE INACTIVE -> PARENT

Comments:

In plasma, M1 accounted for 10% of the 14C-radioactivity. In urine, the most abundant 14C-component was M1 (62.7% of dose). In feces, the most abundant 14C-components were M1 and M10, which accounted for 3.34% and 4.26% of the radioactive dose, respectively.

Qualification:

FECAL; PLASMA; URINE


					DTM3GJC5NY

4-(3-(4-CARBAMOYL-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-4-OXO-2-THIOXO-IMIDAZOLIDIN-1-YL)-2-FLUORO-BENZOIC ACID

METABOLITE -> PARENT

Comments:

In urine, M10 was a minor metabolite, which accounted for 0.67% of the dose. In feces, M10 was one of the most abundant 14C-components, and it accounted for 4.26% of the radioactive dose.

Qualification:

FECAL; URINE


					HZ7ZZC4TC6

4-(3-(4-(AMINOCARBONYL)-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-4-OXO-2-THIOXO-1-IMIDAZOLIDINYL)-2-FLUORO-N-METHYLBENZAMIDE

METABOLITE -> PARENT

Comments:

Metabolite M7 was trace component in plasma; accounting for ≤ 2% of the radioactivity in the 6- and 24-hour postdose plasma samples and not detected at any other time point. In urine, M7 accounted for 9.45% of the radioactive dose. In feces, M7 accounted for 1.12% of the radioactive dose.

Qualification:

FECAL; PLASMA; URINE


					KLY798P76T

BENZAMIDE, 4-(3-(4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)-5,5-DIMETHYL-4-OXO-2-THIOXO-1-IMIDAZOLIDINYL)-2-FLUORO-N-(HYDROXYMETHYL)-

METABOLITE -> PARENT

Comments:

Trace amount of M6 was observed in urine (≤ 0.42% of the dose) and plasma (≤ 2% of the radioactivity in the 6- and 24-hour postdose plasma samples and not detected at any other time point).

Interaction Type:

MINOR

Qualification:

PLASMA; URINE

Related Record Type Details


					74K9JK886T

DEFLUORO ENZALUTAMIDE

IMPURITY -> PARENT

Amount:


					Q6F84UZ2HZ

O-METHYL (4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)CARBAMOTHIOATE

IMPURITY -> PARENT

Amount:


					HP6388MX6K

4-ISOTHIOCYANATO-2-(TRIFLUOROMETHYL)BENZONITRILE

IMPURITY -> PARENT

Amount:

Related Record Type Details


					93T0T9GKNU

ENZALUTAMIDE

ACTIVE MOIETY

Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	5.8 days [2.8 to 10.2] (average)	SINGLE ORAL DOSE 160 mg (average)

Tmax	PHARMACOKINETIC	1 hours [0.5 to 3] (average)	DOSE 160 mg (average) ORAL ADMINISTRATION

Volume of Distribution	PHARMACOKINETIC	1.57 Liters/Kilogram (average)

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Overview

OverviewOther

Drug as perpetrator​

Drug as victim

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PubMed

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C_max

T_1/2

F_unbound

Drug as perpetrator