DT-Web

DB05266 - Ibudilast


Identification
Name Ibudilast
Accession Number DB05266
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 230.3055
Groups approved
Monoisotopic Weight 230.141913208
Pharmacology
Indication For the treatment of multiple sclerosis, asthma, and cerebrovascular disease.
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
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Gene Name PDE4A
Pharmacological action yes
Actions inhibitor
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
DTHybrid score Not Available
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Gene Name PDE4B
Pharmacological action yes
Actions inhibitor
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
DTHybrid score Not Available
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Gene Name PDE4C
Pharmacological action yes
Actions inhibitor
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
DTHybrid score Not Available
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Gene Name PDE4D
Pharmacological action unknown
Actions inhibitor
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
DTHybrid score Not Available
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Name cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Gene Name PDE3A
Pharmacological action unknown
Actions inhibitor
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
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
16 Adenosine A1 receptor ADORA1 0.1418
1178 Adenosine A2a receptor ADORA2A 0.1277
779 High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A PDE7A 0.1228
691 cAMP-specific 3',5'-cyclic phosphodiesterase 7B PDE7B 0.1163
695 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A PDE10A 0.0879
4200 Cytochrome P450 1A2 CYP1A2 0.0815
268 Adenosine A2b receptor ADORA2B 0.0805
6216 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A PDE8A 0.0701
3806 cGMP-dependent 3',5'-cyclic phosphodiesterase PDE2A 0.0693
4122 Histone deacetylase 2 HDAC2 0.0648
777 Tumor necrosis factor TNF 0.061
6217 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B PDE8B 0.0588
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.055
2684 Histidine triad nucleotide-binding protein 1 HINT1 0.0463
1792 Tissue-type plasminogen activator PLAT 0.0456
527 Prostacyclin receptor PTGIR 0.0423
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0388
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0375
4512 Cytochrome P450 3A4 CYP3A4 0.0373
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.037
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0367
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0365
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0297
6143 Solute carrier family 22 member 7 SLC22A7 0.0296
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.029
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0287
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.027
1830 5'-nucleotidase NT5E 0.0266
6013 Cytochrome P450 2E1 CYP2E1 0.0253
492 Histamine H1 receptor HRH1 0.0244
3957 Adenosine deaminase ADA 0.0239
390 Adenosine A3 receptor ADORA3 0.0206
4119 Cytochrome P450 2D6 CYP2D6 0.0157
5360 High-affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A PDE9A 0.0149
1898 Cytochrome P450 1B1 CYP1B1 0.0129
2256 cGMP-inhibited 3',5'-cyclic phosphodiesterase B PDE3B 0.0122
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0113
6037 Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6G 0.011
6107 Cytochrome P450 3A7 CYP3A7 0.0108
6024 Cytochrome P450 1A1 CYP1A1 0.0106
851 5'-AMP-activated protein kinase subunit beta-2 PRKAB2 0.0105
388 AMP deaminase 1 AMPD1 0.0105
6136 Multidrug resistance-associated protein 5 ABCC5 0.0104
4118 Cytochrome P450 3A5 CYP3A5 0.0102
4924 Cytochrome P450 2C8 CYP2C8 0.0093
1291 cAMP response element-binding protein CREB1 0.0092
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.0091
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.0091
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.0091
297 Adenylate cyclase type 1 ADCY1 0.0091
4198 Fructose-1,6-bisphosphatase 1 FBP1 0.0088
281 5'-AMP-activated protein kinase subunit beta-1 PRKAB1 0.0087
2164 Multidrug resistance-associated protein 4 ABCC4 0.0087
128 Adenine phosphoribosyltransferase APRT 0.0086
4757 Cytochrome P450 2C9 CYP2C9 0.0085
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0084
6021 Adenosine kinase ADK 0.0081
10 Glycogen phosphorylase, liver form PYGL 0.0081
6016 Cytochrome P450 2C19 CYP2C19 0.0079
1588 Multidrug resistance protein 1 ABCB1 0.0077
5691 DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC rmlC 0.0067
3361 Serpin B5 SERPINB5 0.0067
5694 Transcription antiterminator licT licT 0.0067
56 Delta-aminolevulinic acid dehydratase ALAD 0.0054
2356 Delta-aminolevulinic acid dehydratase hemB 0.0054
3613 Delta-aminolevulinic acid dehydratase hemB 0.0054
3674 Delta-aminolevulinic acid dehydratase hemB 0.0054
2286 Isocitrate dehydrogenase [NADP] icd 0.0051
2302 Isocitrate dehydrogenase [NADP] icd 0.0051
2771 Isocitrate dehydrogenase [NADP] icd 0.0051
4534 Cytohesin-2 CYTH2 0.0048
814 Ryanodine receptor 1 RYR1 0.0048
3668 Maltose-binding periplasmic protein precursor malE 0.0047
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0042
2592 Beta-galactosidase lacZ 0.0042
315 Arginase-1 ARG1 0.004
24 Thymidylate synthase TMP1 0.0033
359 Thymidylate synthase TYMS 0.0033
2626 Thymidylate synthase thyA 0.0033
2729 Thymidylate synthase thyA 0.0033
5352 Thymidylate synthase THYA 0.0033
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.0032
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