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Ibudilast

July 24, 2017
Common Name

Ibudilast Description

Ibudilast is an anti-inflammatory and neuroprotective oral agent which shows an excellent safety profile at 60 mg/day and provides significantly prolonged time-to-first relapse and attenuated brain volume shrinkage in patients with relapsing-remitting (RR) and/or secondary progressive (SP) mlitiple sclerosis (MS). Ibudilast is currently in development in the U.S. (codes: AV-411 or MN-166), but is approved for use as an antiinflammatory in Japan. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source KetasKegg 2-Isopropyl-3-isobutyrylpyrazolo(1,5-a)pyridineHMDB 3-Isobutyryl-2-isopropyl-pyrazolo(1,5-a)pyridineHMDB 3-Isobutyryl-2-isopropylpyrazolo(1,5-a)pyridineHMDB 3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridineHMDB AV-411HMDB EyevinalHMDB I0157_sigmaHMDB IbudilastumHMDB Ke tasHMDB Lopac-I-0157HMDB MN-166HMDB Tocris-1694HMDB UNII-m0TTH61XC5HMDB

Chemical Formlia

C14H18N2O Average Molecliar Weight

230.3055 Monoisotopic Molecliar Weight

230.141913208 IUPAC Name

2-methyl-1-[2-(propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]propan-1-one Traditional Name

ibudilast CAS Registry Number

50847-11-5 SMILES

CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C

InChI Identifier

InChI=1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3

InChI Key

ZJVFLBOZORBYFE-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as pyrazolopyridines. These are compounds containing a pyrazolopyridine skeleton, which consists of a pyrazole fused to a pyridine. Pyrazole is 5-membered ring consisting of three carbon atoms and two adjacent nitrogen centers. Pyridine is a 6-membered ring with four carbon and one nitrogen atoms. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Pyrazolopyridines Direct Parent

Pyrazolopyridines Alternative Parents

  • Aryl alkyl ketones
  • Pyridines and derivatives
  • Vinylogous amides
  • Pyrazoles
  • Heteroaromatic compounds
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Pyrazolopyridine
  • Aryl alkyl ketone
  • Aryl ketone
  • Pyridine
  • Azole
  • Pyrazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Ketone
  • Azacycle
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Bronchodilator Agents
  • Phosphodiesterase Inhibitors
  • Platelet Aggregation Inhibitors
  • Vasodilator Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.79e-01 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.18 mg/mLALOGPS logP3.36ALOGPS logP3.68ChemAxon logS-3.1ALOGPS pKa (Strongest Acidic)16.12ChemAxon pKa (Strongest Basic)1.86ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area34.37 Å2ChemAxon Rotatable Bond Count3ChemAxon Refractivity79.38 m3·mol-1ChemAxon Polarizability26.31 Å3ChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-000w-3910000000-7c4d5c86420e4e74cdb1View in MoNA 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

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05266

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05266

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB05266 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

    3543 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ibudilast NuGOwiki Link

    HMDB15614 Metagene Link

    HMDB15614 METLIN ID

    Not Available PubChem Compound

    3671 PDB ID

    Not Available ChEBI ID

    123745

    Product: Hexamethylenetetramine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Cho Y, Crichlow GV, Vermeire JJ, Leng L, Du X, Hodsdon ME, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis EJ: Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11313-8. doi: 10.1073/pnas.1002716107. Epub 2010 Jun 8. [PubMed:20534506 ]
    2. Rodgers KM, Bercum FM, McCallum DL, Rudy JW, Frey LC, Johnson KW, Watkins LR, Barth DS: Acute neuroimmune modulation attenuates the development of anxiety-like freezing behavior in an animal model of traumatic brain injury. J Neurotrauma. 2012 Jul 1;29(10):1886-97. doi: 10.1089/neu.2011.2273. Epub 2012 Apr 26. [PubMed:22435644 ]
    3. Snider SE, Hendrick ES, Beardsley PM: Glial cell modulators attenuate methamphetamine self-administration in the rat. Eur J Pharmacol. 2013 Feb 15;701(1-3):124-30. doi: 10.1016/j.ejphar.2013.01.016. Epub 2013 Jan 31. [PubMed:23375937 ]

    Enzymes

    General function:
    Involved in catalytic activity
    Specific function:
    Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
    Gene Name:
    PDE3A
    Uniprot ID:
    Q14432
    Molecular weight:
    124978.06
    References
    1. Yamazaki T, Anraku T, Matsuzawa S: Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery. Eur J Pharmacol. 2011 Jan 15;650(2-3):605-11. doi: 10.1016/j.ejphar.2010.10.033. Epub 2010 Oct 29. [PubMed:21036126 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
    Gene Name:
    PDE4B
    Uniprot ID:
    Q07343
    Molecular weight:
    64351.765
    References
    1. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4C
    Uniprot ID:
    Q08493
    Molecular weight:
    79900.795
    References
    1. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4D
    Uniprot ID:
    Q08499
    Molecular weight:
    91114.1
    References
    1. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in 3,5-cyclic-nucleotide phosphodiesterase activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4A
    Uniprot ID:
    P27815
    Molecular weight:
    98142.155
    References
    1. Yagi K, Tada Y, Kitazato KT, Tamura T, Satomi J, Nagahiro S: Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats. Neurosurgery. 2010 Mar;66(3):551-9; discussion 559. doi: 10.1227/01.NEU.0000365771.89576.77. [PubMed:20124930 ]
    2. Yamazaki T, Anraku T, Matsuzawa S: Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery. Eur J Pharmacol. 2011 Jan 15;650(2-3):605-11. doi: 10.1016/j.ejphar.2010.10.033. Epub 2010 Oct 29. [PubMed:21036126 ]
    3. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]

    PMID: 2169951

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