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

General Information of Drug (ID: DMT6E5N)

• Drug Name: ONAPRISTONE Drug Info
• Synonyms: Onapristone; 96346-61-1; Onapristone [INN]; ZK-98299; Onapristonum [Latin]; Onapristona [Spanish]; UNII-H6H7G23O3N; ZK 299; CCRIS 6530; ZK 98299; ZK-299; H6H7G23O3N; C29H39NO3; Onapristone (INN); Onapristonum; Onapristona; (8S,11R,13R,14S,17S)-11-(4-dimethylaminophenyl)-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one; Estra-4,9-dien-3-one, 11-(4-(dimethylamino)phenyl)-17-hydroxy-17-(3-hydroxypropyl)-, (11-beta,13-alpha,17-alpha)-

Indication

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

• Cross-matching ID:
  PubChem CID: 5311505
  CAS Number: CAS 96346-61-1
  TTD Drug ID: DMT6E5N
  INTEDE Drug ID: DR1820

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]
Ethynodiol Diacetate	DMZM84R	Contraception	QA21	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 Glucocorticoid receptor (NR3C1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Selenium	DM25CGV	N. A.	N. A.	Approved	[25]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[26]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_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
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] Clinical pipeline report, company report or official report of Context Therapeutics.
• [2] Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer. 1999 Feb;35(2):214-8.
• [3] Drug-metabolizing enzymes and transporters: expression in the human prostate and roles in prostate drug disposition. J Androl. 2006 Mar-Apr;27(2):138-50.
• [4] Ligand-selective targeting of the glucocorticoid receptor to nuclear subdomains is associated with decreased receptor mobility. Mol Endocrinol. 2005 Jun;19(6):1501-15. doi: 10.1210/me.2005-0050. Epub 2005 Feb 10.
• [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] 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.
• [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] 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.
• [23] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [28] 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.
• [29] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [30] 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.
• [31] 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.