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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:41:56 UTC
HMDB IDHMDB0015614
Secondary Accession Numbers
  • HMDB15614
Metabolite Identification
Common NameIbudilast
DescriptionIbudilast, also known as ketas or AV-411, belongs to the class of organic compounds known as pyrazolopyridines. Pyrazolopyridines 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. Ibudilast (development codes: AV-411 or MN-166) is an anti-inflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE4 subtype to the greatest extent, but also showing significant inhibition of other PDE subtypes. In Japan, ibudilast oral capsules are approved for the treatment of asthma, and for improvement of dizziness secondary to chronic cerebral circulation impairment associated with sequelae of cerebral infarction. Ibudilast is a drug. Ibudilast is a moderately basic compound (based on its pKa). It is unknown if the PDE4-inhibiting properties potentiate the effects of TLR4 inactivation and/or vice versa, despite that some of their effects are shared, such as inflammation reducing properties. TLR4 antagonists theoretically reverse the increase in pain and inflammation caused by most TLR4 agonists, which include many opiate and opioid drugs. This likely plays a large part in its effect, specifically its synergy with opioid drugs, its anti-inflammatory effect, and its own painkilling effect. Ibudilast is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4). Ibudilast has bronchodilator, vasodilator and neuroprotective effects, and is mainly used in the treatment of asthma and stroke. It inhibits platelet aggregation, and may also be useful in the treatment of multiple sclerosis. It may have some use reducing methamphetamine and alcohol addiction. Ibudilast crosses the blood–brain barrier and suppresses glial cell activation. Ibudilast ophthalmic solution is indicated for the treatment of allergic conjunctivitis and hay fever.
Structure
Data?1582753316
Synonyms
ValueSource
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 FormulaC14H18N2O
Average Molecular Weight230.3055
Monoisotopic Molecular Weight230.141913208
IUPAC Name2-methyl-1-[2-(propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]propan-1-one
Traditional Nameibudilast
CAS Registry Number50847-11-5
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 KeyZJVFLBOZORBYFE-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrazolopyridines. Pyrazolopyridines 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrazolopyridines
Sub ClassNot Available
Direct ParentPyrazolopyridines
Alternative Parents
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
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Biological location:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.18 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.18 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity79.38 m³·mol⁻¹ChemAxon
Polarizability26.31 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00ko-9620000000-41b0ba218eb72a30b29cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-1900000000-857f6720dd17fb2547d1Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000w-3910000000-7c4d5c86420e4e74cdb1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1490000000-e05398fd5b7ddcf160e1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9330000000-8fca320ae4500967062fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fr-9200000000-f809e94dd2a3af4982fdSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0190000000-29d8c7d8254601f09a23Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a6r-0940000000-91b751bd446800ac3fe4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0btl-2920000000-e768231925a9299b5328Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05266 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05266 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB05266
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3543
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIbudilast
METLIN IDNot Available
PubChem Compound3671
PDB IDNot Available
ChEBI ID123745
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot 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 ]