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

General Information of Drug (ID: DMWLFGO)

• Drug Name: Methyltestosterone Drug Info
• Synonyms: Android (TN)

Indication

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[1]
Hormone deficiency	5A61.1	Approved	[1]
Hot flushes	GA30	Approved	[1]
Hypogonadism	5A61.0	Approved	[1]
Hypogonadotropic hypogonadism		Approved	[1]
Multiple sclerosis	8A40	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Hypogonadism, male		Investigative	[1]

• Cross-matching ID:
  PubChem CID: 6010
  ChEBI ID: CHEMBL1395
  CAS Number: CAS 58-18-4
  TTD Drug ID: DMWLFGO
  INTEDE Drug ID: DR1064
  ACDINA Drug ID: D00421

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	[6]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[9]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]

Drug(s) Metabolized By Cytochrome P450 2B6 (CYP2B6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[17]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[20]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[21]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[22]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[23]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[24]

Drug(s) Affected By Protein GREB1 (GREB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[25]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[26]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[28]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[29]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[30]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[31]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[26]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[5]
Mestranol	DMG3F94	Contraception	QA21	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[3]
UDP-glucuronosyltransferase 2A1 (UGT2A1)	DEGKRXT	UD2A1_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Gene/Protein Processing	[5]

References

• [1] Methyltestosterone FDA Label
• [2] 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: 6945).
• [3] Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites. J Chromatogr B Biomed Sci Appl. 1999 Nov 26;735(1):73-83.
• [4] Hepatic expression patterns of aryl hydrocarbon receptor, pregnane X receptor, two cytochrome P450s and five phase II metabolism genes responsive to 17alpha-methyltestosterone in rare minnow Gobiocypris rarus. Environ Toxicol Pharmacol. 2014 May;37(3):1157-68.
• [5] Evaluation of an imaging-based in vitro screening platform for estrogenic activity with OECD reference chemicals. Toxicol In Vitro. 2022 Jun;81:105348. doi: 10.1016/j.tiv.2022.105348. Epub 2022 Mar 18.
• [6] 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.
• [7] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [8] 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.
• [9] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [10] 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.
• [11] 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.
• [12] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [13] 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.
• [14] 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.
• [15] Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
• [16] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [17] Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
• [18] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [19] Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
• [20] Drugs that may have potential CYP2B6 interactions.
• [21] Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
• [22] Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
• [23] PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
• [24] Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
• [25] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [26] A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
• [27] Arsenic induces functional re-expression of estrogen receptor by demethylation of DNA in estrogen receptor-negative human breast cancer. PLoS One. 2012;7(4):e35957. doi: 10.1371/journal.pone.0035957. Epub 2012 Apr 27.
• [28] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [29] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [30] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [31] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.