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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
SaltsNot Available
Brand namesNot Available
Brand mixturesNot 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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyrazolopyridines
SubclassNot Available
Direct parentPyrazolopyridines
Alternative parentsPyridines and Derivatives; Pyrazoles; Ketones; Polyamines; Enolates
Substituentspyridine; azole; pyrazole; ketone; enolate; polyamine; organonitrogen compound; carbonyl group
Classification descriptionThis compound belongs to the pyrazolopyridines. These are compounds containing a pyrazolopyridine skeleton, which consists of a pyrazole fused to a pyridine.
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
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9868
Caco-2 permeable + 0.6112
P-glycoprotein substrate Non-substrate 0.788
P-glycoprotein inhibitor I Inhibitor 0.5207
P-glycoprotein inhibitor II Non-inhibitor 0.7071
Renal organic cation transporter Non-inhibitor 0.8179
CYP450 2C9 substrate Non-substrate 0.8076
CYP450 2D6 substrate Non-substrate 0.793
CYP450 3A4 substrate Substrate 0.5476
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Inhibitor 0.6259
CYP450 2C19 substrate Inhibitor 0.8071
CYP450 3A4 substrate Non-inhibitor 0.6338
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7965
Ames test Non AMES toxic 0.7408
Carcinogenicity Non-carcinogens 0.8482
Biodegradation Not ready biodegradable 0.9838
Rat acute toxicity 2.2040 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9554
hERG inhibition (predictor II) Non-inhibitor 0.9088
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.179ALOGPS
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 RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound3671
PubChem Substance99443231
ChemSpider3543
BindingDB50240404
PharmGKBPA165958351
WikipediaIbudilast
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