Identification

Name
Apalutamide
Accession Number
DB11901
Type
Small Molecule
Groups
Approved, Investigational
Description

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 [3]. 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 [3]. 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 [3].

Structure
Thumb
Synonyms
Not Available
External IDs
JNJ-56021927
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ErleadaTablet, film coated60 mg/1OralJanssen Products, LP2018-02-14Not applicableUs
Categories
UNII
4T36H88UA7
CAS number
956104-40-8
Weight
Average: 477.44
Monoisotopic: 477.088258569
Chemical Formula
C21H15F4N5O2S
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

Pharmacology

Indication

Indicated for the treatment of patients with non-metastatic, castration-resistant prostate cancer (NM-CRPC) [Label].

Associated Conditions
Pharmacodynamics

In an open-label, uncontrolled, multi-center, 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 an antitumor activity in the mouse xenograft models of prostate cancer, where it decreased tumor cell proliferation and reduced tumor volume [Label].

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 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 [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) [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 the activity of apalutamide in an in vitro transcriptional reporter assay [Label].

TargetActionsOrganism
AAndrogen receptor
antagonist
Human
UGABA-A receptor (anion channel)
antagonist
Human
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 [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.

Volume of distribution

The mean apparent volume of distribution at steady-state of apalutamide was approximately 276 L [Label].

Protein binding

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

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) [Label].

Half life

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

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. An increase in apparent clearance (CL/F) was observed with repeat dosing, likely due to induction of apalutamide’s own metabolism. The auto-induction effect likely reached its maximum at the recommended dosage because exposure of apalutamide across the dose range of 30 to 480 mg is dose-proportional [Label].

Toxicity

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

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 [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 [Label].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe serum concentration of 16-Bromoepiandrosterone can be decreased when it is combined with Apalutamide.
19-norandrostenedioneThe serum concentration of 19-norandrostenedione can be decreased when it is combined with Apalutamide.
5-androstenedioneThe serum concentration of 5-androstenedione can be decreased when it is combined with Apalutamide.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Apalutamide.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Apalutamide.
AcebutololThe serum concentration of Acebutolol can be decreased when it is combined with Apalutamide.
AceclofenacThe serum concentration of Aceclofenac can be decreased when it is combined with Apalutamide.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Apalutamide.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Apalutamide.
Acetyl sulfisoxazoleThe serum concentration of Acetyl sulfisoxazole can be decreased when it is combined with Apalutamide.
Food Interactions
Not Available

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. [PubMed:27160947]
  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. [PubMed:22266222]
  3. FDA Press Announcements: FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint [Link]
External Links
PubChem Compound
24872560
PubChem Substance
347828234
ChemSpider
28424131
BindingDB
50094975
ChEMBL
CHEMBL3183409
Wikipedia
Apalutamide
FDA label
Download (233 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCastration-Resistant Prostate Cancer (CRPC)1
1Active Not RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer / Metastatic Castration-Resistant Prostate Cancer (mCRPC) / Prostatic Neoplasms1
1Active Not RecruitingTreatmentProstate Cancer1
1Active Not RecruitingTreatmentProstatic Neoplasms, Castration-Resistant2
1CompletedTreatmentHealthy Volunteers3
1Not Yet RecruitingTreatmentProstatic Neoplasms1
1RecruitingTreatmentCastration-Resistant Prostatic Neoplasms1
1RecruitingTreatmentHepatic Impairment1
1RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer1
1RecruitingTreatmentProstatic Neoplasms1
2Not Yet RecruitingTreatmentAdenocarcinoma of the Prostate / Prostate Cancer1
2Not Yet RecruitingTreatmentAndrogen Antagonists / Neoadjuvant Therapy / Prostate Cancer / Prostatectomy1
2Not Yet RecruitingTreatmentCancer of the Prostate1
2Not Yet RecruitingTreatmentCastration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / PSA Progression / Stage IV Prostate Adenocarcinoma AJCC v71
2Not Yet RecruitingTreatmentProstate Cancer2
2Not Yet RecruitingTreatmentProstatic Neoplasms, Castration-Resistant1
2RecruitingTreatmentCastration-Resistant Prostate Cancer (CRPC) / Metastatic Castration Resistant Prostate Cancer1
2RecruitingTreatmentDiseases of Male Genital Organs / Prostate Cancer1
2RecruitingTreatmentLow Risk Prostate Cancer1
2RecruitingTreatmentNewly Diagnosed Oligometastatic Prostate Cancer1
2RecruitingTreatmentPSA Progression / Stage III Prostate Adenocarcinoma / Stage IV Prostate Adenocarcinoma1
2RecruitingTreatmentProstate Cancer10
2RecruitingTreatmentStage II Prostate Adenocarcinoma / Stage II Prostate Adenocarcinoma AJCC v71
2RecruitingTreatmentStage III Prostate Adenocarcinoma / Stage III Prostate Adenocarcinoma AJCC v7 / Stage III Prostate Cancer / Stage III Prostate Cancer AJCC v7 / Stage IV Prostate Adenocarcinoma / Stage IV Prostate Adenocarcinoma AJCC v7 / Stage IV Prostate Cancer / Stage IV Prostate Cancer AJCC v71
2WithdrawnTreatmentProstatic Neoplasms, Castration-Resistant1
3Active Not RecruitingTreatmentProstate Cancer1
3Active Not RecruitingTreatmentProstatic Neoplasms2
3Not Yet RecruitingTreatmentProstate Cancer1
3RecruitingTreatmentProstate Cancer1
3RecruitingTreatmentProstatic Neoplasms2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral60 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9481663No2013-06-042033-06-04Us
US8802689No2007-03-272027-03-27Us
US8445507No2010-09-152030-09-15Us
US9884054No2013-09-232033-09-23Us
US9388159No2007-03-272027-03-27Us

Properties

State
Solid
Experimental Properties
Not Available
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Phenylimidazolidine / Alpha-amino acid or derivatives / N-phenylthiourea / 2-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Benzoyl / Fluorobenzene / Halobenzene
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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. [PubMed:22266222]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
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. [PubMed:22266222]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:29626324]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:29626324]
  2. Apalutamide FDA Label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Apalutamide FDA label [File]
  2. Erleada (apalutamide) monograph [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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

Transporters

Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
In vitro, apalutamide and N-desmethyl apalutamide inhibit multidrug and toxin extrusions (MATEs).
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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

Drug created on October 20, 2016 14:58 / Updated on September 13, 2018 16:02