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

General Information of Drug (ID: DMC4RK7)

• Drug Name: MX-4509 Drug Info
• Synonyms: 17alpha-Estradiol; 57-91-0; Alfatradiol; Epiestradiol; 17-alpha-Estradiol; 3,17-Dihydroxyestratriene; 17a-estradiol; Estradiol-17alpha; Epiestrol; 17-Epiestradiol; Estra-1,3,5(10)-triene-3,17alpha-diol; 17alpha estradiol; NSC 20293; UNII-3VQ38D63M7; Alfatradiol [INN]; Oestradiol-17alpha; 17alpha-Oestradiol; Estradiol, 17alpha-; CHEBI:17160; VOXZDWNPVJITMN-SFFUCWETSA-N; 3VQ38D63M7; 17-epi-Estradiol; Alfatradiol (INN); Oestradiol-17-alpha; MITO-4509; Parkinsons therapeutics, MitoKor; Drug screening (Parkinsons), MitoKor; Estrogen analogs (Parkinsons), Mitokor

Indication

Disease Entry	ICD 11	Status	REF
Neurological disorder	6B60	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 68570
  ChEBI ID: CHEMBL286452
  CAS Number: CAS 57-91-0
  TTD Drug ID: DMC4RK7

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]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[13]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[14]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[16]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[17]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[17]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[17]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[18]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[19]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[20]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[21]

Drug(s) Affected By Protein GREB1 (GREB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[22]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[23]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[25]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[23]
Nandrolone	DMFWKG1	Osteoporosis	FB83.0	Approved	[4]
Mestranol	DMG3F94	Contraception	QA21	Approved	[23]

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]
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Gene/Protein Processing	[4]

References

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• [3] Review of the effects of 17alpha-estradiol in humans: a less feminizing estrogen with neuroprotective potential. Article first published online: 9 FEB 2009.
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• [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.
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• [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] 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.
• [14] 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.
• [15] Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
• [16] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [19] 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: 620).
• [20] Clinical pipeline report, company report or official report of Shionogi (2011).
• [21] Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.
• [22] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [27] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [28] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.