DrugBank: Ibudilast (DB05266)

targets (5)

Identification

Name

Ibudilast

Accession Number

DB05266

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

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
I0157_SIGMA
Ibudilast (jan/inn)
Ibudilast [inn:jan]
Ibudilastum
Ibudilastum [latin]
Ke tas
Ketas
Ketas (TN)
Lopac-I-0157
MN-166
Pyrazolo(1,5-a)pyridine, 3-isobutyryl-2-isopropyl-
Tocris-1694
UNII-M0TTH61XC5

Salts

Not Available

Brand names

Not Available

Brand mixtures

Not Available

Categories

Vasodilator Agents
Platelet Aggregation Inhibitors
Phosphodiesterase Inhibitors
Bronchodilator Agents

CAS number

50847-11-5

Weight

Average: 230.3055
Monoisotopic: 230.141913208

Chemical Formula

C₁₄H₁₈N₂O

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

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

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.

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

Toxicity

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

Affected organisms

Humans and other mammals

Pathways

Not Available

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

Property	Value	Source
water solubility	1.79e-01 g/l	ALOGPS
logP	3.36	ALOGPS
logP	3.68	ChemAxon
logS	-3.1	ALOGPS
pKa (strongest acidic)	16.12	ChemAxon
pKa (strongest basic)	1.86	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	2	ChemAxon
hydrogen donor count	0	ChemAxon
polar surface area	34.37	ChemAxon
rotatable bond count	3	ChemAxon
refractivity	79.38	ChemAxon
polarizability	26.31	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	3671
PubChem Substance	99443231
ChemSpider	3543
BindingDB	50240404
PharmGKB	PA165958351
Wikipedia	http://en.wikipedia.org/wiki/Ibudilast

ATC Codes

R03DC04

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. cAMP-specific 3',5'-cyclic phosphodiesterase 4A Pharmacological action: yes Actions: inhibitor Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate Organism class: human UniProt ID: P27815 Gene: PDE4A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 Pharmacological action: yes Actions: inhibitor May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents Organism class: human UniProt ID: Q07343 Gene: PDE4B Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Pharmacological action: yes Actions: inhibitor Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate Organism class: human UniProt ID: Q08493 Gene: PDE4C Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Pharmacological action: unknown Actions: inhibitor Regulates the levels of cAMP in the cell Organism class: human UniProt ID: Q08499 Gene: PDE4D Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Pharmacological action: unknown Actions: inhibitor Hydrolyzes both cyclic AMP (cAMP) and cyclic GMP (cGMP) Organism class: human UniProt ID: Q14432 Gene: PDE3A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Targets

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

Pharmacological action: yes
Actions: inhibitor

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: P27815 Link_out

Gene: PDE4A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

Pharmacological action: yes
Actions: inhibitor

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

Organism class: human
UniProt ID: Q07343 Link_out

Gene: PDE4B Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: yes
Actions: inhibitor

Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate

Organism class: human
UniProt ID: Q08493 Link_out

Gene: PDE4C Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: unknown
Actions: inhibitor

Regulates the levels of cAMP in the cell

Organism class: human
UniProt ID: Q08499 Link_out

Gene: PDE4D Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: unknown
Actions: inhibitor

Hydrolyzes both cyclic AMP (cAMP) and cyclic GMP (cGMP)

Organism class: human
UniProt ID: Q14432 Link_out

Gene: PDE3A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on November 18, 2007 11:22 / Updated on February 08, 2013 16:24