Details of the Drug

General Information of Drug (ID: DMRZLU4)

Drug Name
BAY 86-5044
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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 508.5
Topological Polar Surface Area (xlogp) 4.5
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C28H29F5O3
IUPAC Name
(8S,11R,13S,14S,17S)-11-(4-acetylphenyl)-17-hydroxy-13-methyl-17-(1,1,2,2,2-pentafluoroethyl)-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one
Canonical SMILES
CC(=O)C1=CC=C(C=C1)[C@H]2C[C@]3([C@@H](CC[C@]3(C(C(F)(F)F)(F)F)O)[C@H]4C2=C5CCC(=O)C=C5CC4)C
InChI
InChI=1S/C28H29F5O3/c1-15(34)16-3-5-17(6-4-16)22-14-25(2)23(11-12-26(25,36)27(29,30)28(31,32)33)21-9-7-18-13-19(35)8-10-20(18)24(21)22/h3-6,13,21-23,36H,7-12,14H2,1-2H3/t21-,22+,23-,25-,26-/m0/s1
InChIKey
VHZPUDNSVGRVMB-RXDLHWJPSA-N
Cross-matching ID
PubChem CID
6918548
CAS Number
211254-73-8
TTD ID
D0L3HU

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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.