Ibudilast

Identification

Generic Name
Ibudilast
DrugBank Accession Number
DB05266
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 230.3055
Monoisotopic: 230.141913208
Chemical Formula
C14H18N2O
Synonyms
  • Ibudilast
  • Ibudilastum
External IDs
  • AV-411
  • AV411
  • BRN 0656579
  • MN-166

Pharmacology

Indication

For the treatment of multiple sclerosis, asthma, and cerebrovascular disease.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Ibudilast 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.

TargetActionsOrganism
A3',5'-cyclic-AMP phosphodiesterase 4A
inhibitor
Humans
A3',5'-cyclic-AMP phosphodiesterase 4B
inhibitor
Humans
A3',5'-cyclic-AMP phosphodiesterase 4C
inhibitor
Humans
U3',5'-cyclic-AMP phosphodiesterase 4D
inhibitor
Humans
UcGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

19 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe risk or severity of hypotension can be increased when Ibudilast is combined with Abaloparatide.
AbciximabThe risk or severity of bleeding can be increased when Ibudilast is combined with Abciximab.
AbrocitinibThe risk or severity of bleeding and thrombocytopenia can be increased when Ibudilast is combined with Abrocitinib.
AcebutololIbudilast may increase the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of bleeding can be increased when Aceclofenac is combined with Ibudilast.
Food Interactions
Not Available

Products

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International/Other Brands
Ke Tas / Ketas

Categories

ATC Codes
R03DC04 — Ibudilast
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrazolopyridines
Sub Class
Not Available
Direct Parent
Pyrazolopyridines
Alternative Parents
Aryl alkyl ketones / Pyridines and derivatives / Vinylogous amides / Pyrazoles / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Ketone / Organic nitrogen compound / Organic oxide
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
M0TTH61XC5
CAS number
50847-11-5
InChI Key
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

References

General References
Not Available
Human Metabolome Database
HMDB0015614
PubChem Compound
3671
PubChem Substance
99443231
ChemSpider
3543
BindingDB
50240404
ChEBI
31684
ChEMBL
CHEMBL19449
ZINC
ZINC000000004234
PharmGKB
PA165958351
PDBe Ligand
AVL
Wikipedia
Ibudilast
PDB Entries
4grq

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
3RecruitingTreatmentMyelopathy / Spinal Cord Diseases1somestatusstop reasonjust information to hide
2CompletedBasic ScienceOpioid Related Disorders1somestatusstop reasonjust information to hide
2CompletedOtherOpioid Abuse / Opioid Dependence1somestatusstop reasonjust information to hide
2CompletedTreatmentAlcohol Use Disorders (AUD)2somestatusstop reasonjust information to hide
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.179 mg/mLALOGPS
logP3.36ALOGPS
logP3.68Chemaxon
logS-3.1ALOGPS
pKa (Strongest Acidic)16.55Chemaxon
pKa (Strongest Basic)1.85Chemaxon
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
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00ko-9620000000-41b0ba218eb72a30b29c
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-1900000000-857f6720dd17fb2547d1
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000w-3910000000-7c4d5c86420e4e74cdb1
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0090000000-d31808f4bc2e2030dd4c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0090000000-cd2106cbee2f05addbbd
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0690000000-059b0336e238e7191c78
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03e9-1390000000-e55ce8c1d1d75297d283
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0007-0900000000-118a037df17452ea213d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01vk-2900000000-bd8df0bd904e6d271403
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-164.5806291
predicted
DarkChem Lite v0.1.0
[M-H]-164.6116291
predicted
DarkChem Lite v0.1.0
[M-H]-157.7118
predicted
DeepCCS 1.0 (2019)
[M+H]+165.5125291
predicted
DarkChem Lite v0.1.0
[M+H]+165.7095291
predicted
DarkChem Lite v0.1.0
[M+H]+160.06982
predicted
DeepCCS 1.0 (2019)
[M+Na]+164.8398291
predicted
DarkChem Lite v0.1.0
[M+Na]+166.16298
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4A
Uniprot ID
P27815
Uniprot Name
3',5'-cyclic-AMP phosphodiesterase 4A
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:15260978). May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
3',5'-cyclic-AMP phosphodiesterase 4B
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4C
Uniprot ID
Q08493
Uniprot Name
3',5'-cyclic-AMP phosphodiesterase 4C
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE4D
Uniprot ID
Q08499
Uniprot Name
3',5'-cyclic-AMP phosphodiesterase 4D
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099)
Specific Function
3',5'-cyclic-AMP phosphodiesterase activity
Gene Name
PDE3A
Uniprot ID
Q14432
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
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. [Article]

Drug created at November 18, 2007 18:22 / Updated at January 14, 2023 19:02