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Lubiprostone

July 24, 2017
Common Name

Lubiprostone Description

Lubiprostone is a medication used in the management of idiopathic chronic constipation. It is a bicyclic fatty acid (prostaglandin E1 derivative) which acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source AmitizaKegg RU-0211HMDB 0211, SPIMeSH

Chemical Formlia

C20H32F2O5 Average Molecliar Weight

390.4619 Monoisotopic Molecliar Weight

390.221780544 IUPAC Name

7-[(2R,4aR,5S,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxo-octahydrocyclopenta[b]pyran-5-yl]heptanoic acid Traditional Name

lubiprostone CAS Registry Number

136790-76-6 SMILES

[H][C@@]12CC(=O)[C@@H](CCCCCCC(O)=O)[C@@]1([H])CC[C@@](O)(O2)C(F)(F)CCCC

InChI Identifier

InChI=1S/C20H32F2O5/c1-2-3-11-19(21,22)20(26)12-10-15-14(16(23)13-17(15)27-20)8-6-4-5-7-9-18(24)25/h14-15,17,26H,2-13H2,1H3,(H,24,25)/t14-,15+,17+,20+/m0/s1

InChI Key

WGFOBBZOWHGYQH-DKYLXPRQSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid. Kingdom

Chemical entities Super Class

Organic compounds Class

Lipids and lipid-like moleclies Sub Class

Fatty Acyls Direct Parent

Prostaglandins and related compounds Alternative Parents

  • Medium-chain fatty acids
  • Hydroxy fatty acids
  • Heterocyclic fatty acids
  • Halogenated fatty acids
  • Oxanes
  • Hemiacetals
  • Fluorohydrins
  • Cyclic ketones
  • Oxacyclic compounds
  • Monocarboxylic acids and derivatives
  • Carboxylic acids
  • Organofluorides
  • Organic oxides
  • Hydrocarbon derivatives
  • Alkyl fluorides

    • Substituents

  • Prostaglandin skeleton
  • Medium-chain fatty acid
  • Halogenated fatty acid
  • Heterocyclic fatty acid
  • Hydroxy fatty acid
  • Oxane
  • Fatty acid
  • Fluorohydrin
  • Halohydrin
  • Hemiacetal
  • Ketone
  • Cyclic ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Organohalogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Alkyl halide
  • Alkyl fluoride
  • Organic oxygen compound
  • Organofluoride
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound

    • Molecliar Framework

    Aliphatic heteropolycyclic compounds External Descriptors

  • prostanoid (CHEBI:34945 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-constipation Agents
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability

    • Application

  • Nutrients
  • Pharmaceutical
  • Stabilizers
  • Surfactants and Emlisifiers

    • Cellliar locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.56e-02 g/LNot Available LogP4.3Not Available

    Predicted Properties

    Property Value Source Water Solubility0.026 mg/mLALOGPS logP2.76ALOGPS logP4.56ChemAxon logS-4.2ALOGPS pKa (Strongest Acidic)4.3ChemAxon pKa (Strongest Basic)-4.4ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count5ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area83.83 Å2ChemAxon Rotatable Bond Count11ChemAxon Refractivity95.6 m3·mol-1ChemAxon Polarizability41.52 Å3ChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01046

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01046

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01046 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    571057 KEGG Compound ID

    C13707 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Lubiprostone NuGOwiki Link

    HMDB15180 Metagene Link

    HMDB15180 METLIN ID

    Not Available PubChem Compound

    656719 PDB ID

    Not Available ChEBI ID

    Not Available

    Product: Thio-TEPA

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Lacy BE, Chey WD: Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. Expert Opin Pharmacother. 2009 Jan;10(1):143-52. doi: 10.1517/14656560802631319 . [PubMed:19236188 ]
    2. Lacy BE, Levy LC: Lubiprostone: a novel treatment for chronic constipation. Clin Interv Aging. 2008;3(2):357-64. [PubMed:18686757 ]
    3. Crowell MD, Harris LA, DiBaise JK, Olden KW: Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation. Curr Opin Investig Drugs. 2007 Jan;8(1):66-70. [PubMed:17263187 ]
    4. Ambizas EM, Ginzburg R: Lubiprostone: a chloride channel activator for treatment of chronic constipation. Ann Pharmacother. 2007 Jun;41(6):957-64. Epub 2007 May 22. [PubMed:17519292 ]

    Enzymes

    General function:
    Involved in oxidoreductase activity
    Specific function:
    NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.
    Gene Name:
    CBR1
    Uniprot ID:
    P16152
    Molecular weight:
    30374.73
    References
    1. Lacy BE, Chey WD: Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. Expert Opin Pharmacother. 2009 Jan;10(1):143-52. doi: 10.1517/14656560802631319 . [PubMed:19236188 ]
    2. Lacy BE, Levy LC: Lubiprostone: a novel treatment for chronic constipation. Clin Interv Aging. 2008;3(2):357-64. [PubMed:18686757 ]
    General function:
    Involved in voltage-gated chloride channel activity
    Specific function:
    Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport
    Gene Name:
    CLCN2
    Uniprot ID:
    P51788
    Molecular weight:
    98534.4
    References
    1. Authors unspecified: Lubiprostone: RU 0211, SPI 0211. Drugs R D. 2005;6(4):245-8. [PubMed:15991886 ]
    2. Moeser AJ, Nighot PK, Engelke KJ, Ueno R, Blikslager AT: Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G647-56. Epub 2006 Oct 19. [PubMed:17053162 ]
    3. Lacy BE, Levy LC: Lubiprostone: a chloride channel activator. J Clin Gastroenterol. 2007 Apr;41(4):345-51. [PubMed:17413599 ]
    4. Crowell MD, Harris LA, DiBaise JK, Olden KW: Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation. Curr Opin Investig Drugs. 2007 Jan;8(1):66-70. [PubMed:17263187 ]
    5. Lacy BE, Chey WD: Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. Expert Opin Pharmacother. 2009 Jan;10(1):143-52. doi: 10.1517/14656560802631319 . [PubMed:19236188 ]
    6. Ambizas EM, Ginzburg R: Lubiprostone: a chloride channel activator for treatment of chronic constipation. Ann Pharmacother. 2007 Jun;41(6):957-64. Epub 2007 May 22. [PubMed:17519292 ]
    7. Lacy BE, Levy LC: Lubiprostone: a novel treatment for chronic constipation. Clin Interv Aging. 2008;3(2):357-64. [PubMed:18686757 ]
    8. Johanson JF, Ueno R: Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther. 2007 Jun 1;25(11):1351-61. [PubMed:17509103 ]
    9. Kapoor S: Emerging new therapeutic options for the management of opioid induced constipation. J Pain Palliat Care Pharmacother. 2010 Mar;24(1):98-9. doi: 10.3109/15360280903475593. [PubMed:20345211 ]
    10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 14747616

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