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Identification
NameIbudilast
Accession NumberDB05266
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionIbudilast 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
AbciximabIbudilast may increase the anticoagulant activities of Abciximab.
AbciximabAbciximab may increase the antiplatelet activities of Ibudilast.
AcenocoumarolIbudilast may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Ibudilast is combined with Acetylsalicylic acid.
Acetylsalicylic acidAcetylsalicylic acid may increase the antiplatelet activities of Ibudilast.
AlprostadilAlprostadil may increase the antiplatelet activities of Ibudilast.
AlteplaseIbudilast may increase the anticoagulant activities of Alteplase.
ALX-0081Ibudilast may increase the anticoagulant activities of ALX-0081.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Ibudilast is combined with Aminosalicylic Acid.
AnagrelideIbudilast may increase the anticoagulant activities of Anagrelide.
AnagrelideAnagrelide may increase the antiplatelet activities of Ibudilast.
AncrodIbudilast may increase the anticoagulant activities of Ancrod.
AnistreplaseIbudilast may increase the anticoagulant activities of Anistreplase.
Antithrombin III humanIbudilast may increase the anticoagulant activities of Antithrombin III human.
ApixabanIbudilast may increase the anticoagulant activities of Apixaban.
ArdeparinIbudilast may increase the anticoagulant activities of Ardeparin.
ArgatrobanIbudilast may increase the anticoagulant activities of Argatroban.
ArgatrobanArgatroban may increase the antiplatelet activities of Ibudilast.
AstaxanthinIbudilast may increase the anticoagulant activities of Astaxanthin.
AzelastineAzelastine may increase the antiplatelet activities of Ibudilast.
BatroxobinIbudilast may increase the anticoagulant activities of Batroxobin.
BecaplerminIbudilast may increase the anticoagulant activities of Becaplermin.
BemiparinIbudilast may increase the anticoagulant activities of Bemiparin.
BeraprostIbudilast may increase the anticoagulant activities of Beraprost.
BeraprostBeraprost may increase the antiplatelet activities of Ibudilast.
BivalirudinIbudilast may increase the anticoagulant activities of Bivalirudin.
CangrelorIbudilast may increase the anticoagulant activities of Cangrelor.
CangrelorCangrelor may increase the antiplatelet activities of Ibudilast.
CertoparinIbudilast may increase the anticoagulant activities of Certoparin.
CilostazolIbudilast may increase the anticoagulant activities of Cilostazol.
CilostazolCilostazol may increase the antiplatelet activities of Ibudilast.
Citric AcidIbudilast may increase the anticoagulant activities of Citric Acid.
ClopidogrelIbudilast may increase the anticoagulant activities of Clopidogrel.
ClopidogrelClopidogrel may increase the antiplatelet activities of Ibudilast.
CollagenaseThe risk or severity of adverse effects can be increased when Ibudilast is combined with Collagenase.
Dabigatran etexilateIbudilast may increase the anticoagulant activities of Dabigatran etexilate.
DalteparinIbudilast may increase the anticoagulant activities of Dalteparin.
DanaparoidIbudilast may increase the anticoagulant activities of Danaparoid.
DasatinibDasatinib may increase the anticoagulant activities of Ibudilast.
DefibrotideIbudilast may increase the anticoagulant activities of Defibrotide.
DefibrotideDefibrotide may increase the antiplatelet activities of Ibudilast.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Ibudilast is combined with Deoxycholic Acid.
DesirudinIbudilast may increase the anticoagulant activities of Desirudin.
DesmoteplaseIbudilast may increase the anticoagulant activities of Desmoteplase.
DextranIbudilast may increase the anticoagulant activities of Dextran.
Dextran 40Ibudilast may increase the anticoagulant activities of Dextran 40.
Dextran 70Ibudilast may increase the anticoagulant activities of Dextran 70.
Dextran 75Ibudilast may increase the anticoagulant activities of Dextran 75.
DicoumarolIbudilast may increase the anticoagulant activities of Dicoumarol.
DiflunisalThe risk or severity of adverse effects can be increased when Ibudilast is combined with Diflunisal.
DipyridamoleIbudilast may increase the anticoagulant activities of Dipyridamole.
DipyridamoleDipyridamole may increase the antiplatelet activities of Ibudilast.
DitazoleIbudilast may increase the anticoagulant activities of Ditazole.
Drotrecogin alfaIbudilast may increase the anticoagulant activities of Drotrecogin alfa.
Edetic AcidIbudilast may increase the anticoagulant activities of Edetic Acid.
EdoxabanIbudilast may increase the anticoagulant activities of Edoxaban.
EnoxaparinIbudilast may increase the anticoagulant activities of Enoxaparin.
EpinastineEpinastine may increase the antiplatelet activities of Ibudilast.
EpoprostenolIbudilast may increase the anticoagulant activities of Epoprostenol.
EpoprostenolEpoprostenol may increase the antiplatelet activities of Ibudilast.
EptifibatideIbudilast may increase the anticoagulant activities of Eptifibatide.
EptifibatideEptifibatide may increase the antiplatelet activities of Ibudilast.
Ethyl biscoumacetateIbudilast may increase the anticoagulant activities of Ethyl biscoumacetate.
FibrinolysinIbudilast may increase the anticoagulant activities of Fibrinolysin.
Fondaparinux sodiumIbudilast may increase the anticoagulant activities of Fondaparinux sodium.
GlucosamineGlucosamine may increase the antiplatelet activities of Ibudilast.
HeparinIbudilast may increase the anticoagulant activities of Heparin.
HirulogIbudilast may increase the anticoagulant activities of Hirulog.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Ibudilast is combined with Ibritumomab tiuxetan.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Ibudilast.
Icosapent ethylIbudilast may increase the antiplatelet activities of Icosapent ethyl.
IfenprodilIbudilast may increase the antiplatelet activities of Ifenprodil.
IloprostIbudilast may increase the anticoagulant activities of Iloprost.
IloprostIloprost may increase the antiplatelet activities of Ibudilast.
LepirudinIbudilast may increase the anticoagulant activities of Lepirudin.
LimaprostLimaprost may increase the antiplatelet activities of Ibudilast.
MesalazineThe risk or severity of adverse effects can be increased when Ibudilast is combined with Mesalazine.
MilrinoneMilrinone may increase the antiplatelet activities of Ibudilast.
NadroparinIbudilast may increase the anticoagulant activities of Nadroparin.
NCX 4016Ibudilast may increase the anticoagulant activities of NCX 4016.
NCX 4016NCX 4016 may increase the antiplatelet activities of Ibudilast.
NimesulideNimesulide may increase the antiplatelet activities of Ibudilast.
ObinutuzumabThe risk or severity of adverse effects can be increased when Ibudilast is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Ibudilast.
OtamixabanIbudilast may increase the anticoagulant activities of Otamixaban.
ParnaparinIbudilast may increase the anticoagulant activities of Parnaparin.
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Ibudilast.
Pentosan PolysulfateIbudilast may increase the anticoagulant activities of Pentosan Polysulfate.
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Ibudilast.
PhenindioneIbudilast may increase the anticoagulant activities of Phenindione.
PhenprocoumonIbudilast may increase the anticoagulant activities of Phenprocoumon.
PlasminIbudilast may increase the anticoagulant activities of Plasmin.
PrasugrelIbudilast may increase the anticoagulant activities of Prasugrel.
PrasugrelPrasugrel may increase the antiplatelet activities of Ibudilast.
Protein CIbudilast may increase the anticoagulant activities of Protein C.
ProtocatechualdehydeIbudilast may increase the anticoagulant activities of Protocatechualdehyde.
ResveratrolResveratrol may increase the antiplatelet activities of Ibudilast.
ReteplaseIbudilast may increase the anticoagulant activities of Reteplase.
ReviparinIbudilast may increase the anticoagulant activities of Reviparin.
RidogrelRidogrel may increase the antiplatelet activities of Ibudilast.
RiociguatIbudilast may increase the hypotensive activities of Riociguat.
RivaroxabanIbudilast may increase the anticoagulant activities of Rivaroxaban.
RosiglitazoneIbudilast may increase the anticoagulant activities of Rosiglitazone.
Salicylic acidThe risk or severity of adverse effects can be increased when Ibudilast is combined with Salicylic acid.
SCH-530348Ibudilast may increase the antiplatelet activities of SCH-530348.
SelexipagIbudilast may increase the anticoagulant activities of Selexipag.
SevofluraneSevoflurane may increase the antiplatelet activities of Ibudilast.
SRT501SRT501 may increase the antiplatelet activities of Ibudilast.
StreptokinaseIbudilast may increase the anticoagulant activities of Streptokinase.
SulodexideIbudilast may increase the anticoagulant activities of Sulodexide.
TenecteplaseIbudilast may increase the anticoagulant activities of Tenecteplase.
TesmilifeneTesmilifene may increase the antiplatelet activities of Ibudilast.
TicagrelorIbudilast may increase the anticoagulant activities of Ticagrelor.
TiclopidineIbudilast may increase the anticoagulant activities of Ticlopidine.
TiclopidineTiclopidine may increase the antiplatelet activities of Ibudilast.
TinzaparinIbudilast may increase the anticoagulant activities of Tinzaparin.
TipranavirTipranavir may increase the antiplatelet activities of Ibudilast.
TirofibanIbudilast may increase the anticoagulant activities of Tirofiban.
TirofibanTirofiban may increase the antiplatelet activities of Ibudilast.
TositumomabThe risk or severity of adverse effects can be increased when Ibudilast is combined with Tositumomab.
TranilastIbudilast may increase the antiplatelet activities of Tranilast.
TrapidilIbudilast may increase the antiplatelet activities of Trapidil.
TreprostinilIbudilast may increase the anticoagulant activities of Treprostinil.
TreprostinilTreprostinil may increase the antiplatelet activities of Ibudilast.
TriflusalIbudilast may increase the anticoagulant activities of Triflusal.
TriflusalTriflusal may increase the antiplatelet activities of Ibudilast.
UrokinaseIbudilast may increase the anticoagulant activities of Urokinase.
Vitamin EVitamin E may increase the antiplatelet activities of Ibudilast.
VorapaxarIbudilast may increase the anticoagulant activities of Vorapaxar.
VorapaxarVorapaxar may increase the antiplatelet activities of Ibudilast.
WarfarinIbudilast may increase the anticoagulant activities of Warfarin.
XimelagatranIbudilast may increase the anticoagulant activities of Ximelagatran.
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 ]
Comments
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Drug created on November 18, 2007 11:22 / Updated on August 17, 2016 12:24