General
Preferred name
apalutamide
Synonyms
ARN-509 ()
ARN 509 ()
Apalutamide?(ARN-509) ()
ARN-509Benzamide, 4-[7-[6-cyano-5-(trifluoromethyl)-3-pyridinyl]-8-oxo-6-thioxo-5,7-diazaspiro-[3.4]oct-5-yl]-2-fluoro-N-methyl- ()
JNJ-56021927 ()
Apalutamida ()
Erleada ()
Apalutamide ()
P&D ID
PD010552
CAS
956104-40-8
Tags
available
drug
Approved by
FDA
PMDA
EMA
First approval
2018
Drug indication
Acute myeloid leukaemia
prostate adenocarcinoma
Prostate cancer
Drug Status
approved
investigational
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
Persistent androgen receptor (AR) signaling is a common feature of castration-resistant prostate cancer (CRPC), attributed to AR gene-amplification, AR gene mutation, increased AR expression or increased androgen biosynthesis in prostate tumors [A31852]. Apalutamide is an antagonist of AR that to the binding-site in the ligand-binding domain of the receptor with the IC50 of 16 nM. Upon binding, apalutamide disrupts AR signalling, inhibits DNA binding, and impedes AR-mediated gene transcription [FDA Label]. Apalutamide impairs the translocation of AR from the cytoplasm to the nucleus thus reduces the concentrations of AR available to interact with the androgen response-elements (AREs) [A31852]. Upon treatment with apalutamide, AR was not recruited to the DNA promoter-regions [A31852]. ; ; Its main metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of apalutamide in an in vitro transcriptional reporter assay [FDA Label].
METABOLISM
Apalutamide primarily undergoes CYP2C8 and CYP3A4-mediated metabolism to its pharmacologically active metabolite, N-desmethyl apalutamide. The contribution of CYP2C8 and CYP3A4 in the total metabolism of apalutamide is approximately 58% and and 13% following single dose but changes to 40% and 37%, respectively at steady-state [FDA Label]. The auto-induction of CYP3A4-mediated metabolism by apalutamide may explain the increase in CYP3A4 enzymatic activity at steady-state. ; ; Based on systemic exposure, relative potency, and pharmacokinetic properties, N-desmethyl apalutamide likely contributed to the clinical activity of apalutamide [FDA Label].
DESCRIPTION
Apalutamide is a novel androgen receptor (AR) antagonist (antiandrogen) that is approved as a treatment for castration-resistant prostate cancer (CRPC) . This compound (91) was discovered in a structure/activity relationship-guided medicinal chemistry program designed to identify antiandrogens devoid of agonistic activity in the setting of androgen receptor overexpression .
(GtoPdb)
DESCRIPTION
Apalutamide is a novel androgen receptor (AR) antagonist (antiandrogen) being investigated as a potential treatment for castration-resistant prostate cancer (CRPC) . This compound (91) was discovered in a structure/activity relationship-guided medicinal chemistry program designed to identify antiandrogens devoid of agonistic activity in the setting of androgen receptor overexpression .
TOXICITY
In the event of an overdose, discontinue apalutamide and undertake general supportive measures until clinical toxicity has been diminished or resolved [FDA Label]. No antidote is currently known of or available for counteracting overdoses of this agent.; ; Apalutamide was not shown to be mutagenic in the bacterial reverse mutation (Ames) assay and was not genotoxic in either in vitro chromosome aberration assay or the in vivo rat bone marrow micronucleus assay or the in vivo rat Comet assay. The carcinogenic potential of the drug has not been evaluated. In repeat-dose toxicity studies in male rats and dogs, atrophy of the prostate gland and seminal vesicles, aspermia/hypospermia, tubular degeneration and/or hyperplasia or hypertrophy of the interstitial cells in the reproductive system were observed at doses 0.9-1.4 times the human exposure based on AUC [FDA Label]. In a fertility study of male rats, a decrease in sperm concentration and motility, increased abnormal sperm morphology, lower copulation and fertility rates in addition to reduced weights of the secondary sex glands and epididymis were observed following 4 weeks of dosing at ⥠25 mg/kg/day [FDA Label].
ABSORPTION
Mean absolute oral bioavailability was approximately 100%. Median time to achieve peak plasma concentration (tmax) was 2 hours (range: 1 to 5 hours). Median tmax may be increased with a high-fat meal. Administration of oral apalutamide at recommended dosages resulted in a steady state within 4 weeks with a maximum peak concentration (Cmax) and AUC of 6.0 mcg/mL and 100 mcg·h/mL, respectively [FDA Label]. Cmax and AUC of apalutamide is expected to increase in a dose-proportional manner. The mean mean peak-to-trough ratio was 1.63 indicating low daily fluctuations in the plasma concentrations of the drug. ; ; The major active metabolite N-desmethyl apalutamide Cmax was 5.9 mcg/mL (1.0) and AUC was 124 mcg·h/mL (23) at steady-state after the recommended dosage.
DESCRIPTION
Apalutamide (ARN-509) is a potent and competitive androgen receptor (AR) antagonist, binding AR with an IC50 of 16 nM[1].
PRICE
121
DESCRIPTION
Apalutamide is an androgen receptor inhibitor used to treat non metastatic, castration resistant prostate cancer.
(Enamine Bioactive Compounds)
DESCRIPTION
Apalutamide (ARN-509) is a small molecule androgen receptor (AR) antagonist with potential antineoplastic activity.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
0
Compound Sets
22
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine Bioactive Compounds
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
31
Molecular Weight
477.09
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
4
Aromatic Ring Count
2
cLogP
3.53
TPSA
89.33
Fraction CSP3
0.29
Chiral centers
0.0
Largest ring
6.0
QED
0.54
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Androgen Receptor
GABAR
Androgen antagonist
Indication
prostate cancer
MOA
Androgen Receptor antagonist
Pathway
Endocrinology/Hormones
Membrane Transporter/Ion Channel
Neuroscience
Vitamin D Related/Nuclear Receptor
Source data
