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

General Information of Drug (ID: DMF0NQR)

Drug Name

Eplerenone Drug Info

Synonyms

Epoxymexrenone; Inspra; Selara; CGP-30083; Inspra (TN); SC-66110; Eplerenone (JAN/USAN/INN); Inspra, Epoxymexrenone, CGP30083, SC-66110,Eplerenone; 7alpha-methoxycarbonyl-3-oxo-9,11alpha-epoxy-17alpha-pregn-4-ene-21,17-carbolactone

Indication

Disease Entry	ICD 11	Status	REF
Heart failure	BD10-BD13	Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]

Therapeutic Class

Antihypertensive Agents

Cross-matching ID

PubChem CID: 443872
ChEBI ID: CHEBI:31547
CAS Number: CAS 107724-20-9
TTD Drug ID: DMF0NQR
INTEDE Drug ID: DR0592
ACDINA Drug ID: D00235

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Mineralocorticoid receptor (MR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aldosterone	DM9S2JW	Hypertension	BA00-BA04	Approved	[6]
Fludrocortisone	DMUDIR8	Addison disease	5A74.0	Approved	[7]
Desoxycorticosterone Acetate	DMS0AFE	Discovery agent	N.A.	Approved	[3]
Desoxycorticosterone Pivalate	DMSA4B3	Addison disease	5A74.0	Approved	[8]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[9]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[3]
Finerenone	DMM4FJ3	Chronic kidney disease	GB61	Approved	[10]
ZK-91587	DMJ94L0	Cardiovascular disease	BA00-BE2Z	Phase 2	[11]
Nerenone	DMBJ3GL	Diabetic nephropathy	GB61.Z	Phase 2	[12]
LY-2623091	DMFGNB4	Chronic kidney disease	GB61	Phase 2	[13]
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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]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[32]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[33]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[34]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[35]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[35]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[36]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[37]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[38]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[39]
Phenelzine	DMHIDUE	Depression	6A70-6A7Z	Approved	[40]
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Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[28]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[30]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[31]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[26]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[32]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[37]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[37]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[41]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[42]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[43]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[44]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[45]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[46]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[47]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mineralocorticoid receptor (MR)	TT26PHO	MCR_HUMAN	Modulator	[3]
HUMAN mineralocorticoid receptor (MR)	TT9P1CK	MCR_HUMAN	Antagonist	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Regulation of Drug Effects	[5]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Regulation of Drug Effects	[5]

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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: 2876).
2	Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14.
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
4	Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Heart Dis. 2003 Sep-Oct;5(5):354-63.
5	The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
6	Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005 Nov 24;243(1-2):35-42.
7	Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans. J Gerontol A Biol Sci Med Sci. 2003 Oct;58(10):B900-5.
8	Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51.
9	Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78.
10	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11	ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus. Life Sci. 1988;43(19):1537-43.
12	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. (Target id: 626).
13	Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):417-24.
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	Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
24	Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
25	Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
26	Drug Interactions Flockhart Table
27	Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
28	Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
29	Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
30	Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
31	Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
32	Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
33	Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
34	The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
35	Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
36	Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
37	Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
38	Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
39	Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.
40	Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
41	Contribution of CYP3A5 to hepatic and renal ifosfamide N-dechloroethylation. Drug Metab Dispos. 2005 Jul;33(7):1074-81. doi: 10.1124/dmd.104.002279. Epub 2005 Apr 8.
42	Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.
43	Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity. J Toxicol Sci. 2017;42(3):343-348.
44	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
45	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
46	Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines. Drug Metab Dispos. 2013 Feb;41(2):281-90.
47	Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line. Am J Respir Cell Mol Biol. 2000 Mar;22(3):360-6.