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Details

Stereochemistry ACHIRAL
Molecular Formula C21H16F4N4O2S
Molecular Weight 464.436
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENZALUTAMIDE

SMILES

CNC(=O)C1=C(F)C=C(C=C1)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
Stereochemistry ACHIRAL
Additional Stereochemistry
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

2012
68
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7464
Prostatic Neoplasms, Castration-Resistant
 21.4 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Androgen Receptor
Approved
7888
XTANDI
Approved (off-label)
8
PubMed

PubMed

TitleDatePubMed
Development of a second-generation antiandrogen for treatment of advanced prostate cancer.
2009 May 8
Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists.
2011 Nov 10
Inhibitors of androgen receptor activation function-2 (AF2) site identified through virtual screening.
2011 Sep 22
Androgen receptor promotes ligand-independent prostate cancer progression through c-Myc upregulation.
2013
NF-κB2/p52 induces resistance to enzalutamide in prostate cancer: role of androgen receptor and its variants.
2013 Aug
Enzalutamide in metastatic prostate cancer before chemotherapy.
2014 Jul 31
Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer.
2014 Jun 12
Molecular alterations and emerging targets in castration resistant prostate cancer.
2014 Mar
Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies.
2015 Jul 13
LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer.
2015 Oct 6
Patents

Patents

20070004753
2
20070254933
1
20080139634
1
20100172975
1
8524755
2

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
Created
by admin
on Mon Oct 21 22:18:36 UTC 2019
Edited
by admin
on Mon Oct 21 22:18:36 UTC 2019
Record UNII
93T0T9GKNU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENZALUTAMIDE
DASH   INN   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
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
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 [WHO-DD]
Common Name English
ENZALUTAMIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C146993
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
NDF-RT N0000175560
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
LIVERTOX 354
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
WHO-ATC L02BB04
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
Code System Code Type Description
IUPHAR
6812
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
PUBCHEM
15951529
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
NDF-RT
N0000185507
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY Cytochrome P450 2C9 Inducers [MoA]
ChEMBL
CHEMBL1082407
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
DRUG BANK
DB08899
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
INN
9621
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
MESH
C540278
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
EVMPD
SUB77412
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
CAS
915087-33-1
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
RXCUI
1307298
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY RxNorm
NDF-RT
N0000185607
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY Cytochrome P450 2C19 Inducers [MoA]
NDF-RT
N0000185506
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY Cytochrome P450 3A4 Inducers [MoA]
NCI_THESAURUS
C71744
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
MERCK INDEX
M11683
Created by admin on Mon Oct 21 22:18:36 UTC 2019 , Edited by admin on Mon Oct 21 22:18:36 UTC 2019
PRIMARY
Related Record Type Details
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
ANDROGEN RECEPTOR F876L
TARGET -> INHIBITOR RESISTANT
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
Structure of HC-1119
LABELED -> NON-LABELED
CYTOCHROME P450 3A5
METABOLIC ENZYME -> INHIBITOR
ANDROGEN RECEPTOR
TARGET -> AGONIST
BINDING
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
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.
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
CYTOCHROME P450 2B6
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 2D6
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 2C9
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
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.
CYTOCHROME P450 1A2
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
ANDROGEN RECEPTOR F876L
TARGET -> AGONIST
ANDROGEN RECEPTOR
TARGET -> INHIBITOR
CYTOCHROME P450 2C9
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided
STRONG
CYTOCHROME P450 2C8
METABOLIC ENZYME -> INHIBITOR
Related Record Type Details
Structure of ENZALUTAMIDE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE ORAL DOSE

Tmax PHARMACOKINETIC DOSE

ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
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