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

General Information of Drug (ID: DMFN07X)

• Drug Name: Nilutamide Drug Info
• Synonyms: Anandron; Nilandron; Nilandrone; Nilutamida; Nilutamidum; Aventis Behring Brand of Nilutamide; Aventis Brand of Nilutamide; Hoechst Brand of Nilutamide; Nilutamida [Spanish]; Nilutamidum [Latin]; N 8534; RU 23908; Anandron (TN); RU 23908-10; RU-23908; Nilutamide (USAN/INN); Nilutamide [USAN:BAN:INN]; Nilutamide [USAN:INN:BAN]; 1-(3'-Trifluoromethyl-4'-nitrophenyl)-4,4-dimethylimidazolidine-2,5-dione; 5,5-Dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-2,4-imidazolidinedione; 5,5-Dimethyl-3-(alpha,alpha,alpha-trifluoro-4-nitro-m-tolyl)hydantoin; 5,5-Dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione; 5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-2,4-imidazolidinedione; 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione

Indication

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 4493
  ChEBI ID: CHEMBL1274
  CAS Number: CAS 63612-50-0
  TTD Drug ID: DMFN07X
  INTEDE Drug ID: DR1158
  ACDINA Drug ID: D00469

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	[5]
Flutamide	DMK0O7U	Prostate cancer	2C82.0	Approved	[6]
Darolutamide	DMV7YFT	Prostate cancer	2C82.0	Approved	[7]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[8]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[9]
Bicalutamide	DMZMSPF	Prostate cancer	2C82.0	Approved	[10]
Fludrocortisone	DMUDIR8	Addison disease	5A74.0	Approved	[11]
ARN-509	DMT81LZ	Acute myeloid leukaemia	2A60	Approved	[12]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[13]
Fluoxymesterone	DMUHCF1	Breast cancer	2C60-2C65	Approved	[14]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[23]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[24]

Drug(s) Metabolized By NADPH-cytochrome P450 reductase (CPR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[25]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[26]
Nitrofurantoin	DM7PQIK	Urinary tract infection	GC08	Approved	[27]
Tacrolimus	DMZ7XNQ	Graft-versus-host disease	4B24	Approved	[28]
Benzphetamine	DMIJATC	Obesity	5B81	Approved	[29]
Menadiol sodium diphosphate	DMP9N85	Coagulation defect	3B10.0	Approved	[30]
Amrubicin	DM6SGUB	Small-cell lung cancer	2C25.Y	Phase 3	[31]
Nitrobenzodiazepine	DM254EW	N. A.	N. A.	Investigative	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Androgen receptor (AR)	TTS64P2	ANDR_HUMAN	Antagonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[3]
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Substrate	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2864).
• [2] 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.
• [3] Nilutamide inhibits mephenytoin 4-hydroxylation in untreated male rats and in human liver microsomes. Xenobiotica. 1991 Dec;21(12):1559-70.
• [4] Generation of free radicals during the reductive metabolism of nilutamide by lung microsomes: possible role in the development of lung lesions in patients treated with this anti-androgen. Biochem Pharmacol. 1992 Feb 4;43(3):654-7.
• [5] Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev. 2004 Apr;3(2):171-87.
• [6] Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [8] Molecular mechanism of androgen action. Trends Endocrinol Metab. 1998 Oct 1;9(8):317-24.
• [9] Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
• [10] Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010 May;121(1):1-11.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [13] 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.
• [14] 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.
• [15] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [16] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [17] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [18] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [19] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [20] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [21] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [22] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [23] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [24] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [25] Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75.
• [26] Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin. Can J Physiol Pharmacol. 1999 Aug;77(8):589-97.
• [27] Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79.
• [28] Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
• [29] On the mechanism of the inactivation of the major phenobarbital-inducible isozyme of rat liver cytochrome P-450 by chloramphenicol. J Biol Chem. 1985 Jul 15;260(14):8397-403.
• [30] Creatinine sulfate/esculoside/hesperidin methyl chalcone/menadiol sodium phosphate/tranexamic acid actions.
• [31] Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride. Xenobiotica. 2005 Dec;35(12):1121-33.
• [32] Flavin-containing reductase: new perspective on the detoxification of nitrobenzodiazepine. Expert Opin Drug Metab Toxicol. 2010 Aug;6(8):967-81.