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

General Information of Drug (ID: DMRZLU4)

• Drug Name: BAY 86-5044 Drug Info
• Synonyms: Lonaprisan; ZK-230211; 211254-73-8; UNII-F5Z5EL4D26; F5Z5EL4D26; AC1OCFKM; ZK-PRA; Lonaprisan [USAN:INN]; Lonaprisan (USAN/INN); SCHEMBL977182; CHEMBL146032; zk230211; BDBM50409115; BAY86-5044; ZK 230211; ZK 232011; D10016; Z-3103; (8S,11R,13S,14S,17S)-11-(4-ACETYLPHENYL)-17-HYDROXY-13-METHYL-17-(PERFLUOROETHYL)-6,7,8,11,12,13,14,15,16,17-DECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-3(2H)-ONE; Lonaprisan

Indication

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

• Cross-matching ID:
  PubChem CID: 6918548
  CAS Number: CAS 211254-73-8
  TTD Drug ID: DMRZLU4

Molecule-Related Drug Atlas

Drug(s) Targeting Progesterone receptor (PGR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Premature labour	JB00	Approved	[4]
Desogestrel	DM27U4Y	Contraception	QA21	Approved	[5]
Ulipristal	DMBNI20	Contraception	QA21	Approved	[6]
Etonogestrel	DMKA8J4	Contraception	QA21	Approved	[7]
Megestrol	DMDH9KX	Breast cancer	2C60-2C65	Approved	[8]
Segesterone acetate; ethinyl estradiol	DMFEGB0	Contraception	QA21	Approved	[9]
Norgestimate	DMYP4XC	Contraception	QA21	Approved	[7]
Dydrogesterone	DMAKIDV	Menstrual disorder	GA20.3	Approved	[10]
Medroxyprogesterone	DMBGWPH	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Ethynodiol diacetate	DMZM84R	Contraception	QA21	Approved	[11]

Drug(s) Targeting Glucocorticoid receptor (NR3C1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexamethasone	DMMWZET	Rheumatoid arthritis	FA20	Approved	[12]
Hydrocortisone	DMGEMB7	Inflammation	1A00-CA43.1	Approved	[13]
Prednisolone	DMQ8FR2	Solid tumour/cancer	2A00-2F9Z	Approved	[14]
Fluticasone	DMGCSVF	Allergic rhinitis	CA08.0	Approved	[15]
Betamethasone valerate	DMMIAXO	Dermatological disease	DA24.Y	Approved	[13]
Methylprednisolone	DM4BDON	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Deflazacort	DMV0RNS	Duchenne dystrophy	8C70	Approved	[13]
Prednisone	DM2HG4X	Inflammation	1A00-CA43.1	Approved	[16]
Budesonide	DMJIBAW	Asthma	CA23	Approved	[17]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[18]

Drug(s) Targeting Androgen receptor messenger RNA (AR mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dihydrotestosterone	DM3S8XC	Prostate hyperplasia	GA90	Phase 4	[19]
TRC-253	DMXI8CD	Prostate cancer	2C82.0	Phase 1/2	[20]
ISIS-AR	DM8P3N5	Prostate cancer	2C82.0	Phase 1	[21]
EZN-4176	DMNPS59	Prostate cancer	2C82.0	Phase 1	[22]
Eugenol	DM7US1H	Discovery agent	N.A.	Patented	[23]
RU-58841	DMMEAZ2	Acne vulgaris	ED80	Discontinued in Phase 1	[24]
Flavone	DMEQH6J	Discovery agent	N.A.	Investigative	[25]
Apigenin	DMI3491	Discovery agent	N.A.	Investigative	[25]
Kaempferol	DMHEMUB	Discovery agent	N.A.	Investigative	[25]
LGD-5552	DM67KWM	Discovery agent	N.A.	Investigative	[26]

Drug(s) Targeting Progesterone (PG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ORG-33628	DMWZXF7	Contraception	QA21	Discontinued in Phase 2	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Androgen receptor messenger RNA (AR mRNA)	TTKPW01	ANDR_HUMAN	Inhibitor	[2]
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Inhibitor	[2]
Progesterone (PG)	TTHL6YX	NOUNIPROTAC	Antagonist	[3]
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT00555919) ZK 230211 in Postmenopausal Woman With Metastatic Breast Cancer. U.S. National Institutes of Health.
• [2] Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J Med Chem. 2000 Dec 28;43(26):5010-6.
• [3] Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer. Ann Oncol. 2013 Oct;24(10):2543-8.
• [4] Clinical pipeline report, company report or official report of lipocine.
• [5] Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
• [8] Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
• [9] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [10] 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.
• [11] 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.
• [12] Interaction between the glucocorticoid and erythropoietin receptors in human erythroid cells. Exp Hematol. 2009 May;37(5):559-72.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [14] Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mice. Laryngoscope. 2000 Nov;110(11):1902-6.
• [15] Fluticasone furoate nasal spray in allergic rhinitis. Drugs Today (Barc). 2008 Apr;44(4):251-60.
• [16] Cytochromes P450 (CYP) in the Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1): dose- and time-dependent glucocorticoid potentiation of CYP1A induction without induction of CYP3A. ArchBiochem Biophys. 1996 May 1;329(1):113-22.
• [17] PXR-mediated induction of human CYP3A4 and mouse Cyp3a11 by the glucocorticoid budesonide. Eur J Pharm Sci. 2009 Mar 2;36(4-5):565-71.
• [18] The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor levels but not on EC50 values. Steroids. 2007 Jun;72(6-7):600-8.
• [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: 628).
• [20] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [21] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
• [22] 2011 Pipeline of Santaris Pharma.
• [23] Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4.
• [24] Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen recepto... J Med Chem. 2008 Nov 13;51(21):7010-4.
• [25] Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10.
• [26] Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9.
• [27] ORG 33628 and ORG 31710 to control vaginal bleeding in progestin-only contraceptive regimens. Semin Reprod Med. 2005 Feb;23(1):101-11.