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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
SynonymLanguageCode
2-Isopropyl-3-isobutyrylpyrazolo(1,5-a)pyridineNot AvailableNot Available
3-isobutyryl-2-isopropylpyrazolo(1,5-a)pyridineNot AvailableNot Available
3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridineNot AvailableNot Available
AV-411Not AvailableNot Available
EyevinalNot AvailableNot Available
IbudilastNot AvailableINN, JAN
IbudilastumLatinNot Available
Ke tasNot AvailableNot Available
KetasNot AvailableNot Available
Ketas (TN)Not AvailableNot Available
MN-166Not AvailableNot Available
Pyrazolo(1,5-a)pyridine, 3-isobutyryl-2-isopropyl-Not AvailableNot Available
Tocris-1694Not AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number50847-11-5
WeightAverage: 230.3055
Monoisotopic: 230.141913208
Chemical FormulaC14H18N2O
InChI KeyZJVFLBOZORBYFE-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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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 substrateNon-inhibitor0.907
CYP450 2D6 substrateInhibitor0.6259
CYP450 2C19 substrateInhibitor0.8071
CYP450 3A4 substrateNon-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
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
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesR03DC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4A P27815 Details

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. Pubmed
  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. 2010 Oct 29. Pubmed
  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

2. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Q07343 Details

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

3. cAMP-specific 3',5'-cyclic phosphodiesterase 4C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4C Q08493 Details

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

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Q08499 Details

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

5. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Q14432 Details

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. 2010 Oct 29. Pubmed

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Drug created on November 18, 2007 11:22 / Updated on September 16, 2013 17:26