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Identification
NameIbudilast
Accession NumberDB05266
TypeSmall Molecule
GroupsApproved, Investigational
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) multiple 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
Thumb
Synonyms
2-Isopropyl-3-isobutyrylpyrazolo(1,5-a)pyridine
3-isobutyryl-2-isopropylpyrazolo(1,5-a)pyridine
3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine
AV-411
Eyevinal
Ibudilast
Ibudilastum
Ke tas
Ketas
Ketas (TN)
MN-166
Pyrazolo(1,5-a)pyridine, 3-isobutyryl-2-isopropyl-
Tocris-1694
External Identifiers
  • I0157_SIGMA
  • Lopac-I-0157
  • UNII-M0TTH61XC5
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIM0TTH61XC5
CAS number50847-11-5
WeightAverage: 230.3055
Monoisotopic: 230.141913208
Chemical FormulaC14H18N2O
InChI KeyInChIKey=ZJVFLBOZORBYFE-UHFFFAOYSA-N
InChI
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
IUPAC Name
2-methyl-1-[2-(propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]propan-1-one
SMILES
CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrazolopyridines
Sub ClassNot Available
Direct ParentPyrazolopyridines
Alternative Parents
Substituents
  • Pyrazolopyridine
  • Aryl alkyl ketone
  • Aryl ketone
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Pyrazole
  • Azole
  • Ketone
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of multiple sclerosis, asthma, and cerebrovascular disease.
PharmacodynamicsNot Available
Mechanism of actionIbudilast has mechanisms that include anti-inflammatory effects, such as phosphodiesterase inhibition, and neuroprotective effects, such as inhibition of [nitric oxide] synthesis and reduction in reactive oxygen species.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life19 hours
ClearanceNot Available
ToxicityNeuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9868
Caco-2 permeable+0.6112
P-glycoprotein substrateNon-substrate0.788
P-glycoprotein inhibitor IInhibitor0.5207
P-glycoprotein inhibitor IINon-inhibitor0.7071
Renal organic cation transporterNon-inhibitor0.8179
CYP450 2C9 substrateNon-substrate0.8076
CYP450 2D6 substrateNon-substrate0.793
CYP450 3A4 substrateSubstrate0.5476
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.6259
CYP450 2C19 inhibitorInhibitor0.8071
CYP450 3A4 inhibitorNon-inhibitor0.6338
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7965
Ames testNon AMES toxic0.7408
CarcinogenicityNon-carcinogens0.8482
BiodegradationNot ready biodegradable0.9838
Rat acute toxicity2.2040 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9554
hERG inhibition (predictor II)Non-inhibitor0.9088
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.179 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
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesR03DC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
RiociguatIbudilast may increase the hypotensive activities of Riociguat.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
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:
83342.695 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ubiquitin protein ligase binding
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
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.
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular Weight:
124978.06 Da
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 ]
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Drug created on November 18, 2007 11:22 / Updated on August 17, 2016 12:24