Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMT81LZ)

• Drug Name: ARN-509 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 24872560
  CAS Number: CAS 956104-40-8
  TTD Drug ID: DMT81LZ
  INTEDE Drug ID: DR0121
  ACDINA Drug ID: D00840

Molecule-Related Drug Atlas

Drug(s) Targeting Androgen receptor (AR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[4]
Flutamide	DMK0O7U	Prostate cancer	2C82.0	Approved	[5]
Darolutamide	DMV7YFT	Prostate cancer	2C82.0	Approved	[6]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[7]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[8]
Bicalutamide	DMZMSPF	Prostate cancer	2C82.0	Approved	[9]
Fludrocortisone	DMUDIR8	Addison disease	5A74.0	Approved	[10]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[11]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[12]
Fluoxymesterone	DMUHCF1	Breast cancer	2C60-2C65	Approved	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[27]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[28]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[24]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[29]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[30]

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]

References

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• [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] Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
• [5] Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [7] Molecular mechanism of androgen action. Trends Endocrinol Metab. 1998 Oct 1;9(8):317-24.
• [8] Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
• [9] Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010 May;121(1):1-11.
• [10] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [11] CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res. 2008 Mar 15;68(6):1715-22.
• [12] Expression of androgen receptor on fibroblast and hepatocyte of rats after deep second-degree burn caused by scalding. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 May;36(3):362-4.
• [13] An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007 Jan;148(1):363-73.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [23] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [24] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [25] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [26] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [27] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [28] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [29] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [30] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.