Apalutamide

Identification

Summary

Apalutamide is an androgen receptor inhibitor used to treat non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer.

Brand Names
Erleada
Generic Name
Apalutamide
DrugBank Accession Number
DB11901
Background

Apalutamide is a potent androgen receptor (AR) antagonist that selectively binds to the ligand-binding domain of AR and blocks AR nuclear translocation or binding to androgen response elements 1. It has been used in trials studying the treatment of Prostate Cancer, Hepatic Impairment, Prostatic Neoplasms, Castration-Resistant Prostate Cancer, and Prostatic Neoplasms, Castration-Resistant, among others. Exerting an antitumor action, apalutamide blocking the effect of androgens that promote tumor growth. It targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets in prostate tumors 1. In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of Bicalutamide or Enzalutamide. Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines 1.

Androgen-deprivation therapy, or hormone therapy, can be used as part of maintenance therapy for patients with non-metastatic prostate cancer. Although most patients achieve therapeutic responses at the initial hormone therapy, many patients progress to non-metastatic castration-resistant (resistance to hormone therapy) prostate cancer which is the second-most common cause of cancer-related deaths in American males 2. Castration-resistant prostate cancer is often incurable, which poses significant clinical challenges for patients. Approximately 10 to 20 % of prostate cancer cases are castration-resistant, and up to 16% of these patients show no evidence of cancer metastasis at the time of castration-resistant diagnosis 5. Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death 1. In a phase-2 multicenter open-label study, 89% of patients with non-metastatic, castration-resistant prostate cancer had ≥50% PSA decline at week 12 of apalutamide treatment 1. In a randomized trial, the median metastasis-free survival for patients taking apalutamide was 40.5 months compared to 16.2 months for patients taking a placebo 5. Apalutamide displayed good tolerability and safety profile in clinical studies.

Apalutamide was approved in February 2018 by the FDA as Erleada for the treatment of patients with non-metastatic prostate cancer that is resistant to treatment with hormone therapy (castration-resistant). It is available as oral tablets. Apalutamide is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer 5.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 477.44
Monoisotopic: 477.088258569
Chemical Formula
C21H15F4N5O2S
Synonyms
  • Apalutamide
External IDs
  • JNJ-56021927

Pharmacology

Indication

Apalutamide is indicated for the treatment of patients with metastatic castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMetastatic castration sensitive prostate cancer••••••••••••••••••
Used as adjunct in combination for therapyMetastatic hormone-sensitive prostate cancer (mhspc)•••••••••••••••••••••••
Treatment ofNon-metastatic castration-resistant prostate cancer••••••••••••••••••••• •••• •• •••••••••• •••••••••• •••••••••••••
Treatment ofNon-metastatic castration-resistant prostate cancer••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

In androgen receptors (AR)-overexpressing LNCaP cells, apaludatamide was reported to have a 7 to 10-fold greater affinity to the AR than bicalutamide.3 Additionally, apalutamide still possesses total antagonistic activity in AR-overexpressing cell lines with bicalutamide-resistance mutations such as T878A and W741C.4 In castrate mice with LNCaP/AR(cs) tumors, apalutamide produced tumor regression (defined by >50% regression in tumor volume) in 8 mice compared to only 1 for bicalutamide.2 The apalutamide-treated tumors also have a 60% decrease in proliferative index and a 10-fold increase in apoptotic rate compared with vehicle.2

In an open-label, uncontrolled, multicenter, single-arm dedicated QT study in 45 patients with CRPC, an exposure-QT analysis suggested a concentration-dependent increase in QTcF for apalutamide and its active metabolite. Apalutamide demonstrated antitumor activity in the mouse xenograft models of prostate cancer, where it decreased tumor cell proliferation and reduced tumor volume.6

Mechanism of action

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.2 Apalutamide is an antagonist of AR that binds directly to the ligand-binding domain of the AR with the IC50 of 16 nM. Upon binding, apalutamide disrupts AR signalling, inhibits DNA binding, and impedes AR-mediated gene transcription.6 Apalutamide impairs the translocation of AR from the cytoplasm to the nucleus thus reducing the concentrations of AR available to interact with the androgen response elements (AREs).2 Upon treatment with apalutamide, AR was not recruited to the DNA promoter regions.2

Its main metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third of the activity of apalutamide in an in vitro transcriptional reporter assay.6

TargetActionsOrganism
AAndrogen receptor
antagonist
Humans
NGABA(A) Receptor
antagonist
Humans
Absorption

Mean absolute oral bioavailability was approximately 100%. The median time to achieve peak plasma concentration (tmax) was 2 hours (range: 1 to 5 hours). 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. Administration of apalutamide to healthy subjects under fasting conditions and with a high-fat meal (approximately 500 to 600 fat calories, 250 carbohydrate calories, and 150 protein calories) resulted in no clinically relevant changes in Cmax and AUC. The median time to reach tmax was delayed approximately 2 hours with food.6

Following administration of the recommended dosage, apalutamide steady-state was achieved after 4 weeks and the mean accumulation ratio was approximately 5-fold. Apalutamide Cmax was 6.0 mcg/mL (1.7) and AUC was 100 mcg·h/mL (32) at steady-state. Daily fluctuations in apalutamide plasma concentrations were low, with the mean peak-to-trough ratio of 1.63.6

Oral administration of four 60 mg apalutamide tablets dispersed in applesauce resulted in no clinically relevant changes in Cmax and AUC compared to the administration of four intact 60 mg tablets under fasting conditions.6

Volume of distribution

The mean apparent volume of distribution at steady state of apalutamide was approximately 276 L.6

Protein binding

Apalutamide was 96% and N-desmethyl apalutamide was 95% bound to plasma proteins with no concentration dependency.6

Metabolism

Metabolism is the main route of elimination of apalutamide. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4 to form active metabolite, N-desmethyl apalutamide. 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.6 The auto-induction of CYP3A4-mediated metabolism by apalutamide may explain the increase in CYP3A4 enzymatic activity at steady-state.6

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Route of elimination

Apalutamide and its main active metabolite are subject to both renal and focal elimination. Up to 70 days following a single oral administration of radiolabeled apalutamide, 65% of the dose was recovered in urine (1.2% of dose as unchanged apalutamide and 2.7% as N-desmethyl apalutamide) and 24% was recovered in feces (1.5% of dose as unchanged apalutamide and 2% as N-desmethyl apalutamide).6

Half-life

The mean effective half-life for apalutamide in patients with NM-CRPC was approximately 3 days at steady-state.6

Clearance

The CL/F of apalutamide was 1.3 L/h after single dosing and increased to 2.0 L/h at steady-state after once-daily dosing likely due to CYP3A4 auto-induction.6 The auto-induction effect likely reached its maximum at the recommended dosage because exposure to apalutamide across the dose range of 30 to 480 mg is dose-proportional.6

Adverse Effects
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Toxicity

There is no known specific antidote for apalutamide overdose. In the event of an overdose, stop apalutamide, undertake general supportive measures until clinical toxicity has been diminished or resolved.6

The safety and efficacy of apalutamide have not been established in females. Based on findings from animals and its mechanism of action, apalutamide can cause fetal harm and loss of pregnancy when administered to a pregnant female. There are no available data on apalutamide use in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of apalutamide to pregnant rats during and after organogenesis resulted in fetal abnormalities and embryo-fetal lethality at maternal exposures ≥ 2 times the human clinical exposure (AUC) at the recommended dose.6

In a 2-year carcinogenicity study in male rats, apalutamide was administered by oral gavage at doses of 5, 15 and 50 mg/kg/day. Apalutamide increased the incidence of Leydig interstitial cell adenoma in the testes at doses ≥ 5 mg/kg/day (0.2 times the human exposure based on AUC). The findings in the testes are considered to be related to the pharmacological activity of apalutamide. Rats are regarded as more sensitive than humans to developing interstitial cell tumors in the testes. Oral administration of apalutamide to male rasH2 transgenic mice for 6 months did not result in increased incidence of neoplasms at doses up to 30 mg/kg/day.6

Apalutamide did not induce mutations 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. In repeat-dose toxicity studies in male rats (up to 26 weeks) and dogs (up to 39 weeks), 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 ≥ 25 mg/kg/day in rats (1.4 times the human exposure based on AUC) and ≥ 2.5 mg/kg/day in dogs (0.9 times the human exposure based on AUC).6

In a fertility study in male rats, a decrease in sperm concentration and motility, increased abnormal sperm morphology, lower copulation and fertility rates (upon pairing with untreated females) along with reduced weights of the secondary sex glands and epididymis were observed following 4 weeks of dosing at ≥ 25 mg/kg/day (0.8 times the human exposure based on AUC). A reduced number of live fetuses due to increased pre- and/or post-implantation loss was observed following 4 weeks of 150 mg/kg/day administration (5.7 times the human exposure based on AUC). Effects on male rats were reversible after 8 weeks from the last apalutamide administration.6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be decreased when it is combined with Apalutamide.
AbacavirAbacavir may decrease the excretion rate of Apalutamide which could result in a higher serum level.
AbametapirThe serum concentration of Apalutamide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Apalutamide can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Apalutamide.
Food Interactions
  • Take at the same time every day.
  • Take with or without food.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ErleadaTablet60 mgOralJanssen Pharmaceuticals2018-07-27Not applicableCanada flag
ErleadaTablet, film coated240 mgOralJanssen Cilag International Nv2023-11-28Not applicableEU flag
ErleadaTablet, film coated60 mgOralJanssen Cilag International Nv2020-12-16Not applicableEU flag
ErleadaTablet240 mgOralJanssen Pharmaceuticals2023-11-01Not applicableCanada flag
ErleadaTablet, film coated60 mg/1OralJanssen Products, LP2018-02-14Not applicableUS flag

Categories

ATC Codes
L02BB05 — Apalutamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylimidazolidines. These are polycyclic compounds containing an imidazoline substituted by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolidines
Sub Class
Imidazolidines
Direct Parent
Phenylimidazolidines
Alternative Parents
2-halobenzoic acids and derivatives / Alpha amino acids and derivatives / N-phenylthioureas / Benzamides / Benzoyl derivatives / Fluorobenzenes / Pyridines and derivatives / Imidazolidinones / Aryl fluorides / Vinylogous halides
show 10 more
Substituents
2-halobenzoic acid or derivatives / Alkyl fluoride / Alkyl halide / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzamide / Benzenoid
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4T36H88UA7
CAS number
956104-40-8
InChI Key
HJBWBFZLDZWPHF-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl}-2-fluoro-N-methylbenzamide
SMILES
CNC(=O)C1=CC=C(C=C1F)N1C(=S)N(C(=O)C11CCC1)C1=CC(=C(N=C1)C#N)C(F)(F)F

References

General References
  1. Smith MR, Antonarakis ES, Ryan CJ, Berry WR, Shore ND, Liu G, Alumkal JJ, Higano CS, Chow Maneval E, Bandekar R, de Boer CJ, Yu MK, Rathkopf DE: 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. Eur Urol. 2016 Dec;70(6):963-970. doi: 10.1016/j.eururo.2016.04.023. Epub 2016 May 6. [Article]
  2. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH: ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. [Article]
  3. Rathkopf DE, Scher HI: Apalutamide for the treatment of prostate cancer. Expert Rev Anticancer Ther. 2018 Sep;18(9):823-836. doi: 10.1080/14737140.2018.1503954. [Article]
  4. Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, Moon M, Maneval EC, Chen I, Darimont B, Hager JH: A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013 Sep;3(9):1020-9. doi: 10.1158/2159-8290.CD-13-0226. Epub 2013 Jun 18. [Article]
  5. FDA Press Announcements: FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint [Link]
  6. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
  7. EMA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Human Metabolome Database
HMDB0248608
PubChem Compound
24872560
PubChem Substance
347828234
ChemSpider
28424131
BindingDB
50094975
RxNav
1999574
ChEMBL
CHEMBL3183409
ZINC
ZINC000043174901
Wikipedia
Apalutamide
FDA label
Download (233 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentNeoplasms of the Prostate1
4RecruitingScreeningMetastatic Castration Sensitive Prostate Cancer (mCSPC)1
3Active Not RecruitingTreatmentNeoplasms of the Prostate4
3Active Not RecruitingTreatmentProstate Cancer3
3RecruitingTreatmentAdenocarcinoma of Prostate / Biochemically Recurrent Prostate Carcinoma / Metastatic Carcinoma of the Prostate / Stage IVB Prostate Cancer AJCC v81

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral240 mg
TabletOral60 mg
TabletOral60.000 mg
Tablet, coatedOral60 mg
Tablet, film coatedOral
Tablet, film coatedOral240 mg/1
Tablet, film coatedOral240 mg
Tablet, film coatedOral60 mg/1
Tablet, film coatedOral60 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9481663No2016-11-012033-06-04US flag
US8802689No2014-08-122027-03-27US flag
US8445507No2013-05-212030-09-15US flag
US9884054No2018-02-062033-09-23US flag
US9388159No2016-07-122027-03-27US flag
US10052314No2018-08-212033-09-23US flag
US9987261No2018-06-052027-03-27US flag
US10849888No2020-12-012033-09-23US flag
US10702508No2020-07-072038-04-30US flag
USRE49353No2013-09-232033-09-23US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitypractically insoluble in aqueous mediaL45538
Predicted Properties
PropertyValueSource
Water Solubility0.00178 mg/mLALOGPS
logP3.05ALOGPS
logP3.46Chemaxon
logS-5.4ALOGPS
pKa (Strongest Acidic)13.05Chemaxon
pKa (Strongest Basic)-0.75Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area89.33 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity113.6 m3·mol-1Chemaxon
Polarizability43.44 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0000900000-b6c2978b61a4c909c43d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0001900000-62189e26573bdc232663
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4j-0002900000-edde52e50f19648bc71b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0001900000-b9e037c5d63941ef3d0d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0umr-0324900000-b47e8767435c3fb7f549
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-08i0-0193200000-cb5e11874b3f9fd8cf31
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-195.70319
predicted
DeepCCS 1.0 (2019)
[M+H]+198.09874
predicted
DeepCCS 1.0 (2019)
[M+Na]+204.01128
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Curator comments
IC50=16 nM
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH: ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Curator comments
Apalutamide exhibits low micromolar affinity (IC50=3.0uM) for the GABAA receptor in radioligand binding-assays.
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, Chen Y, Grillot K, Bischoff ED, Cai L, Aparicio A, Dorow S, Arora V, Shao G, Qian J, Zhao H, Yang G, Cao C, Sensintaffar J, Wasielewska T, Herbert MR, Bonnefous C, Darimont B, Scher HI, Smith-Jones P, Klang M, Smith ND, De Stanchina E, Wu N, Ouerfelli O, Rix PJ, Heyman RA, Jung ME, Sawyers CL, Hager JH: ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503. doi: 10.1158/0008-5472.CAN-11-3948. Epub 2012 Jan 20. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Al-Salama ZT: Apalutamide: First Global Approval. Drugs. 2018 Apr;78(6):699-705. doi: 10.1007/s40265-018-0900-z. [Article]
  2. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Al-Salama ZT: Apalutamide: First Global Approval. Drugs. 2018 Apr;78(6):699-705. doi: 10.1007/s40265-018-0900-z. [Article]
  2. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
  3. Apalutamide FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
  2. Apalutamide FDA label [File]
  3. Erleada (apalutamide) monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
  2. Apalutamide FDA label [File]
  3. Erleada monograph [File]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Patel UJ, Caulfield S: Apalutamide for the Treatment of Nonmetastatic Castration-Resistant Prostate Cancer. J Adv Pract Oncol. 2019 Jul;10(5):501-507. doi: 10.6004/jadpro.2019.10.5.8. Epub 2019 Jul 1. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, apalutamide and N-desmethyl apalutamide inhibit organic cation transporter 2 (OCT2).
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, apalutamide and N-desmethyl apalutamide inhibit organic anion transporter 3 (OAT3).
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, apalutamide and N-desmethyl apalutamide inhibit multidrug and toxin extrusions (MATEs).
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]
  2. Apalutamide FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: ERLEADA® (apalutamide) tablets, for oral use [Link]

Drug created at October 20, 2016 20:58 / Updated at December 05, 2023 12:31