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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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
21.4 nM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
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
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

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
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
TARGET -> INHIBITOR RESISTANT
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
LABELED -> NON-LABELED
METABOLIC ENZYME -> INHIBITOR
TARGET -> AGONIST
BINDING
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.
METABOLIC ENZYME -> INHIBITOR
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
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.
METABOLIC ENZYME -> INHIBITOR
TIME-DEPENDENT INHIBITION
TARGET -> AGONIST
TARGET -> INHIBITOR
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided.
MODERATE
METABOLIC ENZYME -> INDUCER
Therefore, co-administration of enzalutamide with CYP3A4, 2C9, and 2C19 substrates with a narrow therapeutic index should be avoided
STRONG
METABOLIC ENZYME -> INHIBITOR
Related Record Type Details
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