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

General Information of Drug (ID: DMP0OVQ)

• Drug Name: Gestrinone Drug Info
• Synonyms: Dimetrose (TN)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]

• Cross-matching ID:
  PubChem CID: 27812
  ChEBI ID: CHEBI:89642
  CAS Number: CAS 16320-04-0
  TTD Drug ID: DMP0OVQ
  INTEDE Drug ID: DR0771

Molecule-Related Drug Atlas

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[5]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[6]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[6]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[7]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[7]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[7]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[8]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[9]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[10]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[11]

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	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]

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	[21]
Nilutamide	DMFN07X	Prostate cancer	2C82.0	Approved	[21]
Hydroxyflutamide	DMGIZF5	Prostate cancer	2C82.0	Approved	[21]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[22]
Bicalutamide	DMZMSPF	Prostate cancer	2C82.0	Approved	[23]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[24]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[4]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[25]
Selenium	DM25CGV	N. A.	N. A.	Approved	[26]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Adverse drug interactions: a handbook for prescribers. Taylor and Francis group.2010.
• [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] 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.
• [6] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [9] 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).
• [10] Clinical pipeline report, company report or official report of Shionogi (2011).
• [11] 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.
• [12] 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.
• [13] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [14] 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.
• [15] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [16] 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.
• [17] 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.
• [18] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.