Banner
Identification
Name Estropipate
Accession Number DB04574
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Estropipate (usp)
OGEN
Ogen (TN)
Ogen 2.5
Salts Not Available
Brand names
Name Company
Ogen
ORTHO-EST
Brand mixtures Not Available
Categories
  • Hormone Replacement Agents
  • Estrogens
CAS number 7280-37-7
Weight Average: 350.429
Monoisotopic: 350.118794504
Chemical Formula C18H22O5S
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Estropipate 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.
Pharmacodynamics Estropipate 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 action Estradiol 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.
Absorption Estropipate 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 distribution Not Available
Protein binding Not 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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Estropipate
    		Estrone Details
    Estropipate
      		Estriol Details
      Route of elimination Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates
      Half life Not Available
      Clearance Not Available
      Toxicity Not Available
      Affected organisms
      • Humans and other mammals
      Pathways Not Available
      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
      Packagers Not Available
      Dosage forms
      Form Route Strength
      Tablet Oral
      Prices Not Available
      Patents Not Available
      Properties
      State solid
      Experimental Properties Not Available
      Predicted Properties
      Property Value Source
      water solubility 5.90e-03 g/l ALOGPS
      logP 0.29 ALOGPS
      logP 3.83 ChemAxon
      logS -4.8 ALOGPS
      pKa (strongest acidic) -1.7 ChemAxon
      pKa (strongest basic) -7.5 ChemAxon
      physiological charge -1 ChemAxon
      hydrogen acceptor count 4 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 80.67 ChemAxon
      rotatable bond count 2 ChemAxon
      refractivity 89.07 ChemAxon
      polarizability 36.64 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference Not Available
      External Links
      Resource Link
      KEGG Drug D00948 Link_out
      PubChem Compound 5284555 Link_out
      PubChem Substance 46508976 Link_out
      PharmGKB PA165958342 Link_out
      Drug Product Database 2089769 Link_out
      RxList http://www.rxlist.com/ogen-drug.htm Link_out
      PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=oge1308.html&contentName=Ogen&contentId=547 Link_out
      Wikipedia http://en.wikipedia.org/wiki/Estropipate Link_out
      ATC Codes Not Available
      AHFS Codes
      • 68:16.04
      PDB Entries Not Available
      FDA label Not Available
      MSDS Not Available
      Interactions
      Drug Interactions
      Drug Interaction
      Fosphenytoin The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estropipate.
      Griseofulvin The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estropipate.
      Phenobarbital The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estropipate.
      Phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estropipate.
      Prednisolone The estrogenic agent, estropipate, may increase the effect of the corticosteroid, prednisolone.
      Prednisone The estrogenic agent, estropipate, may increase the effect of corticosteroid, prednisone.
      Primidone The enzyme inducer, primidone, decreases the effect of the hormone agent, estropipate.
      Raloxifene Association not recommended
      Food Interactions
      • Take with food to decrease nausea
      Targets

      1. Estrogen receptor

      Pharmacological action: yes
      Actions: agonist

      Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

      Organism class: human
      UniProt ID: P03372 Link_out
      Gene: ESR1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      Pharmacological action: unknown
      Actions: agonist

      Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual

      Organism class: human
      UniProt ID: Q92731 Link_out
      Gene: ESR2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Enzymes

      1. Cytochrome P450 3A4

      Actions: substrate

      Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

      UniProt ID: P08684 Link_out
      Gene: CYP3A4
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      Actions: substrate

      Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

      UniProt ID: P05177 Link_out
      Gene: CYP1A2
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      Actions: inducer

      Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

      UniProt ID: P11712 Link_out
      Gene: CYP2C9
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Transporters

      1. Solute carrier family 22 member 1

      Actions: inhibitor

      Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

      UniProt ID: O15245 Link_out
      Gene: SLC22A1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Carriers

      1. Sex hormone-binding globulin

      Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration

      UniProt ID: P04278 Link_out
      Gene: SHBG Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

      UniProt ID: P02768 Link_out
      Gene: ALB Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. O’Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9 Suppl):18S-24S. Pubmed
      Comments
      Drug created on September 07, 2007 15:12 / Updated on February 08, 2013 16:23