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Risedronate

July 24, 2017
Common Name

Risedronate Description

Risedronate is only found in individuals that have used or taken this drug. It is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Pagets disease of bone.The action of risedronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Risedronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source RidronKegg Risedronic acidGenerator NE-58095HMDB ActonelMeSH 2-(3-Pyridinyl)-1-hydroxyethylidene-bisphosphonateMeSH Risedronate sodiumMeSH 1-Hydroxy-2-(3-pyridyl)ethylidene diphosphonateMeSH AtelviaMeSH Sodium, bisphosphate risedronateMeSH Sodium, risedronateMeSH Bisphosphate risedronate sodiumMeSH 2-(3-Pyridinyl)-1-hydroxyethylidenebisphosphonateMeSH Acid, risedronicMeSH Risedronate sodium, bisphosphateMeSH Risedronic acid, monosodium saltMeSH

Chemical Formlia

C7H11NO7P2 Average Molecliar Weight

283.1123 Monoisotopic Molecliar Weight

283.001074735 IUPAC Name

[1-hydroxy-1-phosphono-2-(pyridin-3-yl)ethyl]phosphonic acid Traditional Name

risedronate CAS Registry Number

105462-24-6 SMILES

OC(CC1=CN=CC=C1)(P(O)(O)=O)P(O)(O)=O

InChI Identifier

InChI=1S/C7H11NO7P2/c9-7(16(10,11)12,17(13,14)15)4-6-2-1-3-8-5-6/h1-3,5,9H,4H2,(H2,10,11,12)(H2,13,14,15)

InChI Key

IIDJRNMFWXDHID-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms. Kingdom

Organic compounds Super Class

Organic acids and derivatives Class

Organic phosphonic acids and derivatives Sub Class

Bisphosphonates Direct Parent

Bisphosphonates Alternative Parents

  • Pyridines and derivatives
  • Organic phosphonic acids
  • Heteroaromatic compounds
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organophosphorus compounds
  • Organooxygen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Bisphosphonate
  • Pyridine
  • Heteroaromatic compound
  • Organophosphonic acid
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organophosphorus compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • pyridines (CHEBI:8869 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antihypocalcemic Agents
  • Antiresorptives
  • Bisphosphonates
  • Bone Density Conservation Agents
  • Calcium Channel Blockers

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.04e+01 g/LNot Available LogP-3.6Not Available

    Predicted Properties

    Property Value Source Water Solubility10.4 mg/mLALOGPS logP-0.75ALOGPS logP-3.3ChemAxon logS-1.4ALOGPS pKa (Strongest Acidic)0.68ChemAxon pKa (Strongest Basic)4.91ChemAxon Physiological Charge-2ChemAxon Hydrogen Acceptor Count8ChemAxon Hydrogen Donor Count5ChemAxon Polar Surface Area148.18 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity57.12 m3·mol-1ChemAxon Polarizability21.91 Å3ChemAxon Number of Rings1ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link Risedronate PathwaySMP00112Not Available

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00884

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00884

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00884 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

    5055 KEGG Compound ID

    C08233 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Risedronate NuGOwiki Link

    HMDB15022 Metagene Link

    HMDB15022 METLIN ID

    Not Available PubChem Compound

    5245 PDB ID

    RIS ChEBI ID

    183772

    Product: HG6-64-2

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in isoprenoid biosynthetic process
    Specific function:
    Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.
    Gene Name:
    FDPS
    Uniprot ID:
    P14324
    Molecular weight:
    48275.03
    References
    1. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G: Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. [PubMed:10620343 ]
    2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    3. Coxon FP, Ebetino FH, Mules EH, Seabra MC, McKenna CE, Rogers MJ: Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone. 2005 Sep;37(3):349-58. [PubMed:16006204 ]
    4. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ: Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42. [PubMed:11160603 ]
    5. Ortiz-Gomez A, Jimenez C, Estevez AM, Carrero-Lerida J, Ruiz-Perez LM, Gonzalez-Pacanowska D: Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Eukaryot Cell. 2006 Jul;5(7):1057-64. [PubMed:16835450 ]
    6. Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH: Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci. 2007 Nov;1117:209-57. [PubMed:18056045 ]
    General function:
    Involved in peroxidase activity
    Specific function:
    Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
    Gene Name:
    PTGS2
    Uniprot ID:
    P35354
    Molecular weight:
    68995.625
    References
    1. Valenti MT, Giannini S, Donatelli L, Zanatta M, Bertoldo F, Sella S, Vilei MT, Ossi E, Realdi G, Lo Cascio V, Dalle Carbonare L: The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation. Arthritis Res Ther. 2010;12(4):R163. doi: 10.1186/ar3122. Epub 2010 Aug 25. [PubMed:20738860 ]

    PMID: 19625493

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