Details of the Drug

General Information of Drug (ID: DMT81LZ)

Drug Name

ARN-509

Synonyms

Arn-509 (AR inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[1]
Prostate cancer	2C82.0	Phase 3	[2]

Affected Organisms

Humans and other mammals

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

477.4

Logarithm of the Partition Coefficient (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 100 mgh/L []
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 6.0 mg/L []
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h []
Bioavailability: The bioavailability of drug is 100% []
Clearance: The clearance of drug is 1.3 L/h []
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) []
Half-life: The concentration or amount of drug in body reduced by one-half in 3 days []
Vd: The volume of distribution (Vd) of drug is 276 L []

Chemical Identifiers

Formula: C21H15F4N5O2S
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
Canonical SMILES: CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F
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)
InChIKey: HJBWBFZLDZWPHF-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 24872560
ChEBI ID: CHEMBL3183409
CAS Number: 956104-40-8
UNII: 4T36H88UA7
DrugBank ID: DB11901
TTD ID: D0S7LG
INTEDE ID: DR0121
ACDINA ID: D00840

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Androgen receptor (AR)	TTS64P2	ANDR_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2C8 (CYP2C8)_{Main DME}	DES5XRU	CP2C8_HUMAN	Substrate	[3]

Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

ICD Disease Classification

02 Neoplasm

Disease Class

ICD-11: 2C82 Prostate cancer

The Studied Tissue

Prostate

The Studied Disease

Prostate cancer [ICD-11:2C82]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Androgen receptor (AR)	DTT	AR	4.81E-01	-0.23	-0.29
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	5.27E-01	-1.74E-02	-6.97E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.10E-01	-1.23E-01	-2.88E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as ARN-509

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Ivosidenib	DM8S6T7	Major	Increased metabolism of Arn-509 caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[4]
Gilteritinib	DMTI0ZO	Major	Increased metabolism of Arn-509 caused by Gilteritinib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[5]

Coadministration of a Drug Treating the Disease Different from ARN-509 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased metabolism of Arn-509 caused by Remdesivir mediated induction of CYP450 enzyme.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[6]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Arn-509 and Levalbuterol.	Asthma [CA23]	[7]
ABT-492	DMJFD2I	Moderate	Increased metabolism of Arn-509 caused by ABT-492 mediated induction of UGT.	Bacterial infection [1A00-1C4Z]	[6]
Erdafitinib	DMI782S	Major	Increased metabolism of Arn-509 caused by Erdafitinib mediated induction of CYP450 enzyme.	Bladder cancer [2C94]	[8]
Pexidartinib	DMS2J0Z	Major	Decreased metabolism of Arn-509 caused by Pexidartinib mediated inhibition of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
LY2835219	DM93VBZ	Major	Increased metabolism of Arn-509 caused by LY2835219 mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[10]
Alpelisib	DMEXMYK	Major	Increased metabolism of Arn-509 caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[11]
PF-04449913	DMSB068	Major	Increased metabolism of Arn-509 caused by PF-04449913 mediated induction of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[12]
MK-8228	DMOB58Q	Moderate	Accelerated clearance of Arn-509 due to the transporter induction by MK-8228.	Cytomegaloviral disease [1D82]	[13]
Polatuzumab vedotin	DMF6Y0L	Minor	Increased metabolism of Arn-509 caused by Polatuzumab vedotin mediated induction of CYP450 enzyme.	Diffuse large B-cell lymphoma [2A81]	[13]
Ingrezza	DMVPLNC	Major	Increased metabolism of Arn-509 caused by Ingrezza mediated induction of CYP450 enzyme.	Dystonic disorder [8A02]	[14]
Bay 80-6946	DMLOS5R	Major	Accelerated clearance of Arn-509 due to the transporter induction by Bay 80-6946.	Follicular lymphoma [2A80]	[15]
Tazemetostat	DMWP1BH	Major	Increased metabolism of Arn-509 caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[16]
Ripretinib	DM958QB	Major	Increased metabolism of Arn-509 caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[17]
Avapritinib	DMK2GZX	Major	Increased metabolism of Arn-509 caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[6]
MK-1439	DM215WE	Major	Increased metabolism of Arn-509 caused by MK-1439 mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[18]
TP-434	DM5A31S	Major	Increased metabolism of Arn-509 caused by TP-434 mediated induction of CYP450 enzyme.	Infectious gastroenteritis/colitis [1A40]	[19]
Pemigatinib	DM819JF	Major	Increased metabolism of Arn-509 caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[6]
Brigatinib	DM7W94S	Major	Increased metabolism of Arn-509 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[20]
Lurbinectedin	DMEFRTZ	Major	Decreased metabolism of Arn-509 caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[21]
PF-06463922	DMKM7EW	Major	Increased metabolism of Arn-509 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[22]
Pralsetinib	DMWU0I2	Major	Increased metabolism of Arn-509 caused by Pralsetinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[23]
Selpercatinib	DMZR15V	Major	Increased metabolism of Arn-509 caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[6]
IPI-145	DMWA24P	Major	Increased metabolism of Arn-509 caused by IPI-145 mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[19]
Ubrogepant	DM749I3	Major	Increased metabolism of Arn-509 caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[24]
Rimegepant	DMHOAUG	Major	Increased metabolism of Arn-509 caused by Rimegepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[25]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Arn-509 and Siponimod.	Multiple sclerosis [8A40]	[13]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Arn-509 and Ozanimod.	Multiple sclerosis [8A40]	[26]
Fedratinib	DM4ZBK6	Major	Increased metabolism of Arn-509 caused by Fedratinib mediated induction of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[6]
Entrectinib	DMMPTLH	Major	Increased metabolism of Arn-509 caused by Entrectinib mediated induction of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[6]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Arn-509 and Rucaparib.	Ovarian cancer [2C73]	[6]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Arn-509 and Triclabendazole.	Parasitic worm infestation [1F90]	[6]
Macimorelin	DMQYJIR	Moderate	Increased metabolism of Arn-509 caused by Macimorelin mediated induction of CYP450 enzyme.	Pituitary gland disorder [5A60-5A61]	[27]
Lefamulin	DME6G97	Major	Increased metabolism of Arn-509 caused by Lefamulin mediated induction of CYP450 enzyme.	Pneumonia [CA40]	[28]
Darolutamide	DMV7YFT	Major	Increased metabolism of Arn-509 caused by Darolutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[29]
Upadacitinib	DM32B5U	Major	Increased metabolism of Arn-509 caused by Upadacitinib mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[30]
Voxelotor	DMCS6M5	Major	Increased metabolism of Arn-509 caused by Voxelotor mediated induction of CYP450 enzyme.	Sickle-cell disorder [3A51]	[31]
Larotrectinib	DM26CQR	Major	Increased metabolism of Arn-509 caused by Larotrectinib mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[13]
Fostamatinib	DM6AUHV	Major	Increased metabolism of Arn-509 caused by Fostamatinib mediated induction of CYP450 enzyme.	Thrombocytopenia [3B64]	[32]
As-1670542	DMV05SW	Moderate	Increased metabolism of Arn-509 caused by As-1670542 mediated induction of CYP450 enzyme.	Thrombocytopenia [3B64]	[6]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Arn-509 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[33]
Fluticasone	DMGCSVF	Moderate	Increased metabolism of Arn-509 caused by Fluticasone mediated induction of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[6]
Betrixaban	DM2C4RF	Moderate	Accelerated clearance of Arn-509 due to the transporter induction by Betrixaban.	Venous thromboembolism [BD72]	[34]


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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferric oxide black	E00522	16211978	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent


⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Apalutamide 60 mg tablet	60 mg	Tablet	Oral

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References

1	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
2	ClinicalTrials.gov (NCT01946204) A Study of ARN-509 in Men With Non-Metastatic Castration-Resistant Prostate Cancer. U.S. National Institutes of Health.
3	Apalutamide: first global approval. Drugs. 2018 Apr;78(6):699-705.
4	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
5	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
6	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
7	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
8	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
9	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
10	Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
11	Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
12	Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
13	Cerner Multum, Inc. "Australian Product Information.".
14	Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
15	Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
16	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
17	Product Information. Qinlock (ripretinib). Deciphera Pharmaceuticals, Waltham, MA.
18	Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
19	Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
20	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
21	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
22	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
23	Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
24	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
25	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
26	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
27	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
28	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
29	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
30	Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.
31	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
32	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
33	Product Information. Orilissa (elagolix). AbbVie US LLC, North Chicago, IL.
34	Gelosa P, Castiglioni L, Tenconi M, et.al "Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs)" Pharmacol Res 135 (2018): 60-79. [PMID: 30040996]