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

General Information of Drug (ID: DMUNG4A)

• Drug Name: Flumethasone Drug Info
• Synonyms: Flucorticin; Flumetasona; Flumetasona [INN-Spanish]; Flumetasone; Flumetasone [INN]; Flumetasonum; Flumetasonum [INN-Latin]; Flumethason; Flumethasonum; Fluvet; LR3CD8SX89; Methagon; RS 2177; RS-2177; U-10974; flumethasone; 2135-17-3; Anaprime; Aniprime; Cortexilar; Flucort (Veterinary); 6-alpha-Fluorodexamethasone; 6alpha,9-Difluoro-11beta,17,21-trihydroxy-16alpha-methylpregna-1,4-diene-3,20-dione; 6alpha,9alpha-Difluoro-16alpha-methylprednisolone; 6alpha-Fluorodexamethasone; CHEBI:34764; MLS000028618; NSC 54702; UNII-LR3CD8SX89

Indication

Disease Entry	ICD 11	Status	REF
Exanthem		Approved	[1]
Granuloma annulare		Approved	[1]
Primary cutaneous T-cell lymphoma		Approved	[1]

• Cross-matching ID:
  PubChem CID: 16490
  ChEBI ID: CHEBI:34764
  CAS Number: CAS 2135-17-3
  TTD Drug ID: DMUNG4A
  INTEDE Drug ID: DR0707

Molecule-Related Drug Atlas

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	[4]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[5]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[6]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[7]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[8]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[9]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[10]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[11]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[5]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[12]

Drug(s) Affected By Glucocorticoid receptor (NR3C1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Selenium	DM25CGV	N. A.	N. A.	Approved	[16]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[17]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[18]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[19]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]

Drug(s) Affected By Mineralocorticoid receptor (NR3C2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[23]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[24]
Triamcinolone	DM98IXF	Acute adrenal insufficiency		Approved	[3]
Aldosterone	DM9S2JW	Hypertension	BA00-BA04	Approved	[25]
Betamethasone	DMAHJEF	Acute adrenal insufficiency		Approved	[3]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[3]
Budesonide	DMJIBAW	Allergic rhinitis	CA08.0	Approved	[3]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[28]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Gene/Protein Processing	[3]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Gene/Protein Processing	[3]

References

• [1] Flumethasone FDA Label
• [2] Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule. BMC Pharmacol. 2010 Jul 16;10:8.
• [3] Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol. 2004 Sep;151(3):397-406. doi: 10.1530/eje.0.1510397.
• [4] 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.
• [5] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [6] 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.
• [7] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [8] 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.
• [9] 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.
• [10] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [11] 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.
• [12] 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.
• [13] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [14] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Comparative effects of microtubules disruption on glucocorticoid receptor functions in proliferating and quiescent cells. Int J Toxicol. 2010 May-Jun;29(3):326-35. doi: 10.1177/1091581810366486.
• [18] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [19] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [20] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [21] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [22] Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14(8):1089-100. doi: 10.3851/IMP1457.
• [23] The human mineralocorticoid receptor only partially differentiates between different ligands after expression in fission yeast. FEMS Yeast Res. 2005 Apr;5(6-7):627-33. doi: 10.1016/j.femsyr.2004.12.007.
• [24] The synthetic androgen methyltrienolone (r1881) acts as a potent antagonist of the mineralocorticoid receptor. Mol Pharmacol. 2007 Feb;71(2):473-82. doi: 10.1124/mol.106.031112. Epub 2006 Nov 14.
• [25] Regulation of mineralocorticoid receptor expression during neuronal differentiation of murine embryonic stem cells. Endocrinology. 2010 May;151(5):2244-54. doi: 10.1210/en.2009-0753. Epub 2010 Mar 5.
• [26] 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.
• [27] 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.
• [28] Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chem Biol Interact. 2009 May 15;179(2-3):288-96.