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

General Information of Drug (ID: DMZM84R)

• Drug Name: Ethynodiol Diacetate Drug Info
• Synonyms: Cervicundin; Continuin; Femulen; Luteonorm; Metrodiol; Ethinodiol diacetate; Ethyndiol Diacetate; Ethynodiol diacetate [Progestins]; Ethynodiol diacetate [USAN]; Etynodiol Acetate; Metrodiol diacetate; Ovulen 50; SC 11800; Etynodiol di(acetate); Luto-metrodiol; SC-11800; Ethynodiol diacetate (JAN/USP);[(3S,8R,9S,10R,13S,14S,17R)-17-acetyloxy-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate; (3 beta, 17 alpha)-19-Norpregn-4-en-20-yne-3,17 diolDiacetate; (3-beta,17-alpha)-19-Norpregn-4-en-20-yne-3,17-diol diacetate; (3beta,17beta)-17-ethynylestr-4-ene-3,17-diyl diacetate; 17-alpha-Ethynyl-19-norandrost-4-ene-3-beta,17-beta-diol diacetate; 17-alpha-Ethynyl-3,17-dihydroxy-4-estrene diacetate; 17-alpha-Ethynyl-4-estrene-3-beta,17-beta-diol diacetate; 17-alpha-Ethynylestr-4-ene-3-beta,17-beta-diol acetate; 17alpha-Ethynyl-19-norandrost-4-ene-3beta,17-beta-diol diacetate; 17alpha-Ethynyl-3,17-dihydroxy-4-estrene diacetate; 17alpha-Ethynyl-4-estrene-3beta,17beta-diol diacetate; 17alpha-Ethynylestr-4-ene-3beta,17beta-diol acetate; 17alpha-ethynylestr-4-ene-3beta,17beta-diyl diacetate; 19-Nor-17-alpha-pregn-4-en-20-yne-3-beta,17-diol diacetate; 19-Nor-17-alpha-pregn-4-en-20-yne-3-beta,17-diol, diacetate; 19-Nor-17alpha-pregn-4-en-20-yne-3beta,17-diol diacetate; 3-beta, 17-beta-Diacetoxy-17-alpha-ethynyl-4-oestrene; 3-beta,17-beta-Diacetoxy-19-nor-17-alpha-pregn-4-en-20-yne; 3beta, 17beta-Diacetoxy-17alpha-ethynyl-4-oestrene; 3beta,17beta-Diacetoxy-17alpha-ethynyl-4-estrene; 3beta,17beta-Diacetoxy-19-nor-17alpha-pregn-4-en-20-yne

Indication

Disease Entry	ICD 11	Status	REF
Contraception	QA21	Approved	[1]

• Therapeutic Class: Contraceptive Agents
• Cross-matching ID:
  PubChem CID: 9270
  ChEBI ID: CHEBI:31580
  CAS Number: CAS 297-76-7
  TTD Drug ID: DMZM84R
  INTEDE Drug ID: DR0663

Molecule-Related Drug Atlas

Drug(s) Targeting Progesterone receptor (PGR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[5]
Desogestrel	DM27U4Y	Contraception	QA21	Approved	[6]
Ulipristal	DMBNI20	Contraception	QA21	Approved	[7]
Etonogestrel	DMKA8J4	Contraception	QA21	Approved	[8]
Megestrol	DMDH9KX	Breast cancer	2C60-2C65	Approved	[9]
Segesterone acetate; ethinyl estradiol	DMFEGB0	Contraception	QA21	Approved	[10]
Norgestimate	DMYP4XC	Acne vulgaris	ED80	Approved	[8]
Dydrogesterone	DMAKIDV	Menstrual disorder	GA20.3	Approved	[11]
Medroxyprogesterone	DMBGWPH	Solid tumour/cancer	2A00-2F9Z	Approved	[11]
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[12]

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	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

Drug(s) Affected By Androgen receptor (AR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[22]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[22]
Hydroxyflutamide	DMGIZF5	Prostate cancer	2C82.0	Approved	[22]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[23]
Bicalutamide	DMZMSPF	Prostate cancer	2C82.0	Approved	[24]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[25]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[4]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[26]
Selenium	DM25CGV	N. A.	N. A.	Approved	[27]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Binder	[2]

Drug-Metabolizing Enzyme (DME)

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

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Protein Interaction/Cellular Processes	[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: 7072).
• [2] Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84.
• [3] News and information in drug research: Ethynodiol diacetate.
• [4] Identifying environmental chemicals as agonists of the androgen receptor by using a quantitative high-throughput screening platform. Toxicology. 2017 Jun 15;385:48-58. doi: 10.1016/j.tox.2017.05.001. Epub 2017 May 4.
• [5] Clinical pipeline report, company report or official report of lipocine.
• [6] Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
• [7] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [8] Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
• [9] Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
• [10] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [11] Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
• [12] Met909 plays a key role in the activation of the progesterone receptor and also in the high potency of 13-ethyl progestins. Mol Pharmacol. 2009 Jun;75(6):1317-24.
• [13] 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.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] 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.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] 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.
• [18] 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.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] 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.
• [21] 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.
• [22] TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer. Toxicol Appl Pharmacol. 2016 Sep 15;307:91-101. doi: 10.1016/j.taap.2016.07.018. Epub 2016 Jul 27.
• [23] Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23.
• [24] Possible role of adaptive mutation in resistance to antiandrogen in prostate cancer cells. Prostate. 2005 Nov 1;65(3):268-75. doi: 10.1002/pros.20282.
• [25] Effects of the environmental estrogens bisphenol A, o,p'-DDT, p-tert-octylphenol and coumestrol on apoptosis induction, cell proliferation and the expression of estrogen sensitive molecular parameters in the human breast cancer cell line MCF-7. J Steroid Biochem Mol Biol. 2002 Jan;80(1):61-70. doi: 10.1016/s0960-0760(01)00173-x.
• [26] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [27] Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. Cancer Res. 2004 Jan 1;64(1):19-22. doi: 10.1158/0008-5472.can-03-2789.
• [28] Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals. Toxicology. 2004 Feb 15;195(2-3):177-86. doi: 10.1016/j.tox.2003.09.012.