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Details

Stereochemistry ACHIRAL
Molecular Formula C21H15F4N5O2S
Molecular Weight 477.435
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APALUTAMIDE

SMILES

CNC(=O)C1=CC=C(C=C1F)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F

InChI

InChIKey=HJBWBFZLDZWPHF-UHFFFAOYSA-N
InChI=1S/C21H15F4N5O2S/c1-27-17(31)13-4-3-11(8-15(13)22)30-19(33)29(18(32)20(30)5-2-6-20)12-7-14(21(23,24)25)16(9-26)28-10-12/h3-4,7-8,10H,2,5-6H2,1H3,(H,27,31)

HIDE SMILES / InChI

Molecular Formula C21H15F4N5O2S
Molecular Weight 477.435
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Apalutamide (developmental code name ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM, useful for prostate cancer treatment. Apalutamide binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells. Apalutamide is currently in phase III clinical trials for castration-resistant prostate cancer.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
16.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ERLEADA
PubMed

PubMed

TitleDatePubMed
ARN-509: a novel antiandrogen for prostate cancer treatment.
2012 Mar 15
New agents for prostate cancer.
2014 Sep
Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort.
2016 Dec
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose of ERLEADA (apalutamide) is 240 mg (four 60 mg tablets) administered orally once daily. Swallow the tablets whole. ERLEADA can be taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
APALUTAMIDE binds AR with IC50 16 nM
Substance Class Chemical
Created
by admin
on Mon Oct 21 22:55:46 UTC 2019
Edited
by admin
on Mon Oct 21 22:55:46 UTC 2019
Record UNII
4T36H88UA7
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APALUTAMIDE
INN   WHO-DD  
INN  
Official Name English
4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)PYRIDIN-3-YL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO(3.4)OCTAN-5-YL)-2-FLUORO-N-METHYLBENZAMIDE
Systematic Name English
ERLEADA
Brand Name English
APALUTAMIDE [INN]
Common Name English
BENZAMIDE, 4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)-3-PYRIDINYL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO(3.4)OCT-5-YL)-2-FLUORO-N-METHYL-
Systematic Name English
JNJ-56021927
Code English
APALUTAMIDE [JAN]
Common Name English
ARN-509
Common Name English
APALUTAMIDE [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ATC L02BB05
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
NCI_THESAURUS C146993
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
Code System Code Type Description
PUBCHEM
24872560
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
INN
10118
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
CAS
956104-40-8
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
EPA CompTox
956104-40-8
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
ChEMBL
CHEMBL3183409
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
NCI_THESAURUS
C92574
Created by admin on Mon Oct 21 22:55:46 UTC 2019 , Edited by admin on Mon Oct 21 22:55:46 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
CUMULATIVE EXCRETION
URINE
BINDER->LIGAND
BINDING
CUMULATIVE EXCRETION
FECAL
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> INDUCER
, coadministration of omeprazole, a CYP2C19 substrate, with multiple daily doses of 240 mg apalutamide decreased the omeprazole AUC by 85%
EXCRETED UNCHANGED
FECAL
TARGET -> INHIBITOR
The binding affinities of apalutamide to the ligand binding domains of AR and PR, and to full-length ER? and GR demonstrate that it is relatively selective for AR (
IC50
TRANSPORTER -> INHIBITOR
IC50
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> INDUCER
coadministration of S-warfarin, a CYP2C9 substrate, with multiple daily doses of 240 mg apalutamide decreased the S-warfarin AUC by 46%
METABOLIC ENZYME -> SUBSTRATE
Due to CYP3A4 auto-induction, the contribution of CYP2C8 and CYP3A4 in the metabolism of apalutamide is estimated to be 58% and 13% following single dose but changes to 40% and 37%, respectively at steady-state.
OFF-TARGET->INHIBITOR
IC50
METABOLIC ENZYME -> INDUCER
coadministration of midazolam, a CYP3A4 substrate, with multiple daily doses of 240 mg apalutamide decreased the midazolam AUC by 92%
Related Record Type Details
METABOLITE ACTIVE -> PARENT
Due to CYP3A4 auto-induction, the contribution of CYP2C8 and CYP3A4 in the metabolism of apalutamide is estimated to be 58% and 13% following single dose but changes to 40% and 37%, respectively at steady-state.
MAJOR
METABOLITE INACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
Due to CYP3A4 auto-induction, the contribution of CYP2C8 and CYP3A4 in the metabolism of apalutamide is estimated to be 58% and 13% following single dose but changes to 40% and 37%, respectively at steady-state.
MAJOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Cmax PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Tmax PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
Tmax PHARMACOKINETIC DOSE
PHARMACOKINETIC
ROUTE OF ADMINISTRATION
PHARMACOKINETIC