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Identification
NameEstropipate
Accession NumberDB04574
Typesmall molecule
Groupsapproved
Description

Estropipate is a form of estrogen. It has several uses such as: Alleviate symptoms of menopause as hormone replacement therapy, treatment some types of infertility, treatment of some conditions leading to underdevelopment of female sexual characteristics,treatment of vaginal atrophy,treatment of some types of breast cancer (particularly in men and postmenopausal women), treatment of prostate cancer and prevention of osteoporosis.

Structure
Thumb
Synonyms
SynonymLanguageCode
EstropipateNot AvailableUSP
OGENNot AvailableNot Available
Ogen (TN)Not AvailableNot Available
Ogen 2.5Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
OgenNot Available
ORTHO-ESTNot Available
Brand mixturesNot Available
Categories
CAS number7280-37-7
WeightAverage: 350.429
Monoisotopic: 350.118794504
Chemical FormulaC18H22O5S
InChI KeyInChIKey=JKKFKPJIXZFSSB-CBZIJGRNSA-N
InChI
InChI=1S/C18H22O5S/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22)/t14-,15-,16+,18+/m1/s1
IUPAC Name
[(1S,10R,11S,15S)-15-methyl-14-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-5-yl]oxidanesulfonic acid
SMILES
C[C@]12CC[C@H]3[C@@H](CCC4=C3C=CC(OS(O)(=O)=O)=C4)[C@@H]1CCC2=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassSulfated Steroids
Direct parentSulfated Steroids
Alternative parentsKetosteroids; Phenanthrenes and Derivatives; Tetralins; Benzene and Substituted Derivatives; Sulfuric Acid Monoesters; Ketones; Polyamines
Substituents17-keto-steroid; phenanthrene; tetralin; sulfuric acid monoester; sulfate-ester; benzene; sulfuric acid derivative; ketone; polyamine; carbonyl group
Classification descriptionThis compound belongs to the sulfated steroids. These are sterol lipids containing a sulfate group attached to the steroid skeleton.
Pharmacology
IndicationEstropipate is used for the treatment of moderate to severe vasomotor symptoms associated with the monopause, and moderate to severe symptoms of vulval and vaginal atrophy associated with the menopause. It is also used to treat hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and prevent postmenopausal osteoporosis.
PharmacodynamicsEstropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Mechanism of actionEstradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.
AbsorptionEstropipate is well absorbed through the skin and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.

SubstrateEnzymesProduct
Estropipate
    EstroneDetails
    Estropipate
      EstriolDetails
      Route of eliminationEstradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates
      Half lifeNot Available
      ClearanceNot Available
      ToxicityNot Available
      Affected organisms
      • Humans and other mammals
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.9974
      Blood Brain Barrier + 0.935
      Caco-2 permeable - 0.8343
      P-glycoprotein substrate Non-substrate 0.5376
      P-glycoprotein inhibitor I Non-inhibitor 0.5591
      P-glycoprotein inhibitor II Non-inhibitor 0.9751
      Renal organic cation transporter Non-inhibitor 0.8407
      CYP450 2C9 substrate Non-substrate 0.7526
      CYP450 2D6 substrate Non-substrate 0.8214
      CYP450 3A4 substrate Substrate 0.6275
      CYP450 1A2 substrate Non-inhibitor 0.9046
      CYP450 2C9 substrate Non-inhibitor 0.9071
      CYP450 2D6 substrate Non-inhibitor 0.923
      CYP450 2C19 substrate Non-inhibitor 0.9026
      CYP450 3A4 substrate Non-inhibitor 0.9421
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8808
      Ames test Non AMES toxic 0.5621
      Carcinogenicity Carcinogens 0.5507
      Biodegradation Not ready biodegradable 0.9558
      Rat acute toxicity 2.2402 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Strong inhibitor 0.5746
      hERG inhibition (predictor II) Inhibitor 0.8077
      Pharmacoeconomics
      Manufacturers
      • Pharmacia and upjohn co
      • Barr laboratories inc
      • Duramed pharmaceuticals inc sub barr laboratories inc
      • Mylan pharmaceuticals inc
      • Watson laboratories inc
      • Sun pharmaceutical industries ltd
      PackagersNot Available
      Dosage forms
      FormRouteStrength
      TabletOral
      PricesNot Available
      PatentsNot Available
      Properties
      Statesolid
      Experimental PropertiesNot Available
      Predicted Properties
      PropertyValueSource
      water solubility5.90e-03 g/lALOGPS
      logP0.29ALOGPS
      logP3.83ChemAxon
      logS-4.8ALOGPS
      pKa (strongest acidic)-1.7ChemAxon
      pKa (strongest basic)-7.5ChemAxon
      physiological charge-1ChemAxon
      hydrogen acceptor count4ChemAxon
      hydrogen donor count1ChemAxon
      polar surface area80.67ChemAxon
      rotatable bond count2ChemAxon
      refractivity89.07ChemAxon
      polarizability36.64ChemAxon
      number of rings4ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis ReferenceNot Available
      General ReferenceNot Available
      External Links
      ResourceLink
      KEGG DrugD00948
      PubChem Compound5284555
      PubChem Substance46508976
      PharmGKBPA165958342
      Drug Product Database2089769
      RxListhttp://www.rxlist.com/ogen-drug.htm
      PDRhealthhttp://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=oge1308.html&contentName=Ogen&contentId=547
      WikipediaEstropipate
      ATC CodesNot Available
      AHFS Codes
      • 68:16.04
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSNot Available
      Interactions
      Drug Interactions
      Drug
      FosphenytoinThe enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estropipate.
      GriseofulvinThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estropipate.
      PhenobarbitalThe enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estropipate.
      PhenytoinThe enzyme inducer, phenytoin, decreases the effect of the hormone agent, estropipate.
      PrednisoloneThe estrogenic agent, estropipate, may increase the effect of the corticosteroid, prednisolone.
      PrednisoneThe estrogenic agent, estropipate, may increase the effect of corticosteroid, prednisone.
      PrimidoneThe enzyme inducer, primidone, decreases the effect of the hormone agent, estropipate.
      RaloxifeneAssociation not recommended
      Food Interactions
      • Take with food to decrease nausea

      1. Estrogen receptor

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: agonist

      Components

      Name UniProt ID Details
      Estrogen receptor P03372 Details

      References:

      1. Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, d’Abusco AS, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. Pubmed
      2. Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. Pubmed
      3. Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. Pubmed
      4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

      2. Estrogen receptor beta

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: agonist

      Components

      Name UniProt ID Details
      Estrogen receptor beta Q92731 Details

      References:

      1. Vijayanathan V, Greenfield NJ, Thomas TJ, Ivanova MM, Tyulmenkov VV, Klinge CM, Gallo MA, Thomas T: Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor beta. Biochem Cell Biol. 2007 Feb;85(1):1-10. Pubmed
      2. Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. Pubmed

      1. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      References:

      1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
      3. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. Pubmed
      4. Williams ET, Leyk M, Wrighton SA, Davies PJ, Loose DS, Shipley GL, Strobel HW: Estrogen regulation of the cytochrome P450 3A subfamily in humans. J Pharmacol Exp Ther. 2004 Nov;311(2):728-35. Epub 2004 Jul 28. Pubmed

      2. Cytochrome P450 1A2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 1A2 P05177 Details

      References:

      1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
      3. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. Pubmed

      3. Cytochrome P450 2C9

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inducer

      Components

      Name UniProt ID Details
      Cytochrome P450 2C9 P11712 Details

      References:

      1. Egnell AC, Eriksson C, Albertson N, Houston B, Boyer S: Generation and evaluation of a CYP2C9 heteroactivation pharmacophore. J Pharmacol Exp Ther. 2003 Dec;307(3):878-87. Epub 2003 Oct 13. Pubmed

      1. Sex hormone-binding globulin

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Sex hormone-binding globulin P04278 Details

      References:

      1. Campusano M C, Brusco G F, Campino J C, Rodriguez P L, Arteaga U E: [Assessment of androgenic decline in the elderly] Rev Med Chil. 2006 Sep;134(9):1123-8. Epub 2006 Dec 12. Pubmed
      2. Kuba R, Pohanka M, Zakopcan J, Novotna I, Rektor I: Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia. 2006 Dec;47(12):2135-40. Pubmed
      3. Bendlova B, Zavadilova J, Vankova M, Vejrazkova D, Lukasova P, Vcelak J, Hill M, Cibula D, Vondra K, Starka L, Vrbikova J: Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):68-74. Epub 2007 Jan 26. Pubmed
      4. Sablik Z, Samborska-Sablik A, Bolinska-Soltysiak H, Goch JH, Kula K: [Hyperandrogenism as a risk factor of coronary artery disease in young women] Pol Arch Med Wewn. 2006 Feb;115(2):118-24. Pubmed
      5. Mohamad MJ, Mohammad MA, Karayyem M, Hairi A, Hader AA: Serum levels of sex hormones in men with acute myocardial infarction. Neuro Endocrinol Lett. 2007 Apr;28(2):182-6. Pubmed
      6. O’Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9 Suppl):18S-24S. Pubmed
      7. Pardridge WM: Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab. 1986 May;15(2):259-78. Pubmed

      2. Serum albumin

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Serum albumin P02768 Details

      References:

      1. O’Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9 Suppl):18S-24S. Pubmed

      1. Solute carrier family 22 member 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 1 O15245 Details

      References:

      1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. Pubmed
      2. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. Pubmed

      Comments
      Drug created on September 07, 2007 15:12 / Updated on September 16, 2013 17:25