Details of the Drug

General Information of Drug (ID: DM78XFG)

• Drug Name: Tibolone
• Synonyms: Livial (TN)

Indication

Disease Entry	ICD 11	Status	REF
Anabolic metabolism	5C50-5C8Z	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 312.4
  Topological Polar Surface Area (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Elimination: 0% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 45 hours [3]
  Metabolism: The drug is metabolized via the liver [3]
• Chemical Identifiers:
  Formula: C21H28O2
  IUPAC Name: (7R,8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-7,13-dimethyl-1,2,4,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
  Canonical SMILES: C[C@@H]1CC2=C(CCC(=O)C2)[C@@H]3[C@@H]1[C@@H]4CC[C@]([C@]4(CC3)C)(C#C)O
  InChI: InChI=1S/C21H28O2/c1-4-21(23)10-8-18-19-13(2)11-14-12-15(22)5-6-16(14)17(19)7-9-20(18,21)3/h1,13,17-19,23H,5-12H2,2-3H3/t13-,17-,18+,19-,20+,21+/m1/s1
  InChIKey: WZDGZWOAQTVYBX-XOINTXKNSA-N
• Cross-matching ID:
  PubChem CID: 444008
  ChEBI ID: CHEBI:32223
  CAS Number: 5630-53-5
  DrugBank ID: DB09070
  TTD ID: D0W3OS
  INTEDE ID: DR1590

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Beta-HSD adrenal and gonadal type (HSD3B2)	DEN0GVQ	3BHS2_HUMAN	Substrate	[4]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Substrate	[5]
Dihydrotestosterone oxidoreductase (HSD3B1)	DERDQWN	3BHS1_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] BDDCS applied to over 900 drugs
• [3] Tibolone for Postmenopausal Women: Systematic Review of Randomized Trials
• [4] Tibolone: a unique version of hormone replacement therapy. Ann Pharmacother. 2004 May;38(5):874-81.
• [5] Sulfation of tibolone metabolites by human postmenopausal liver and small intestinal sulfotransferases (SULTs). Steroids. 2006 May;71(5):343-51.
• [6] Progestagenic effects of tibolone are target gene-specific in human endometrial cells. J Soc Gynecol Investig. 2006 Sep;13(6):459-65.
• [7] Tamoxifen-induced adduct formation and cell stress in human endometrial glands. Drug Metab Dispos. 2010 Jan;38(1):200-7.
• [8] Proposed role of the sulfotransferase/sulfatase pathway in modulating yolk steroid effects. Integr Comp Biol. 2008 Sep;48(3):419-27.
• [9] Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65.
• [10] Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents. Curr Drug Metab. 2006 Oct;7(7):745-53.
• [11] Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine. 2001 Nov;8(6):481-8.
• [12] Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.
• [13] Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. J Endocrinol. 2001 Dec;171(3):525-32.
• [14] Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
• [15] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
• [16] Selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer. J Steroid Biochem Mol Biol. 2011 May;125(1-2):57-65.
• [17] Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity. J Biol Chem. 2002 Nov 8;277(45):42795-801.
• [18] Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab. 2005 Sep;16(7):327-33.
• [19] Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):213-22.