IBUDILAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H18N2O
Molecular Weight	230.3055
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C

InChI

InChIKey=ZJVFLBOZORBYFE-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C14H18N2O
Molecular Weight	230.3055
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607039
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB05266 | https://www.ncbi.nlm.nih.gov/pubmed/27501293

Ibudilast (KETAS®) is a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor. It is an antithrombotic, antiasthmatic drug that is used for improving prognosis and relieving symptoms in patients suffering from ischemic stroke and for the treatment of bronchial asthma. A definitive mechanism of its action is yet to be established. However, inhibition of the release of inflammatory cytokines, inhibition of leukocyte activation, and inhibition of the expression of cell adhesion molecules have been proposed as likely mechanisms of action of ibudilast (KETAS®). It is currently in development in the US (for instance as a potential therapy for multiple sclerosis), but is approved for use in Japan.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 3A 7 Target ID: CHEMBL241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607039	Inhibitor 8297	9.5 µM [Ki]
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607039	Inhibitor 8297	3.3 µM [Ki]
Phosphodiesterase 10A 12 Target ID: CHEMBL4409 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607039	Inhibitor 8297	1.27 µM [Ki]
Phosphodiesterase 11A 3 Target ID: CHEMBL2717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607039	Inhibitor 8297	8.9 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bronchial asthma 50 Sources: http://www.kyorin-pharm.co.jp/prodinfo/medicine/pdf/KETAS_Capsules.pdf	Primary		Approved 8429	KETAS Approved Use 1. Bronchial asthma 2. Improvement of dizziness secondary to chronic cerebral circulation impairment associated with sequelae of cerebral infarction
Cerebral infarction 14 Sources: http://www.kyorin-pharm.co.jp/prodinfo/medicine/pdf/KETAS_Capsules.pdf	Palliative		Approved 8429	KETAS Approved Use 1. Bronchial asthma 2. Improvement of dizziness secondary to chronic cerebral circulation impairment associated with sequelae of cerebral infarction

PubMed

Title	Date	PubMed
Ménière's disease in childhood.	2001 Dec 1	11700197
Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall.	2001 Fall	11607039
Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model.	2001 Jul	11454657
Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development.	2003 Dec	14664469
Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.	2008 Sep 25	18686943
The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse.	2010 Jul 10	20399770
Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast.	2011 Jun 1	21530250

Patents

Sample Use Guides

In Vivo Use Guide

In case of bronchhial asthma: The usual adult dosage for oral use is 10 mg of ibudulast (KETAS®) twice daily. In case of cerebro-vascular disorders: The usual dosage for oral use is 10 mg of ibudulast (KETAS®) three times daily. The dosage may be adjusted according to the patient's symptoms.

Route of Administration: Oral

In Vitro Use Guide

The inhibitory effect of ibudilast against the human phosphodiesterase (PDE) enzyme family was measured. Ibudilast did not exhibit PDE4 subfamily selectivity with Ki values ranging from 3.3 uM to 6.3 uM. Inhibition of PDE10 by ibudilast was essentially the same with cAMP and cGMP as substrates yielding Ki values of 2.2 uM and 1.3 uM, respectively. PDE11 was tested for inhibition using both cAMP and cGMP substrates and cAMP hydrolysis was sensitive to inhibition with a Ki value of 8.9 uM. PDE3A was inhibited by ibudilast with a Ki of 9.5 uM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:37:55 GMT 2023` Edited by `admin` on `Fri Dec 15 15:37:55 GMT 2023`
Record UNII	M0TTH61XC5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IBUDILAST

Official Name

English

AV-411

Code

English

IBUDILAST [MART.]

Common Name

English

KETAS

Brand Name

English

AV411

Code

English

Ibudilast [WHO-DD]

Common Name

English

ibudilast [INN]

Common Name

English

1-(2-ISOPROPYLPYRAZOLO(1,5-.ALPHA.)PYRIDIN-3-YL)-2-METHYL-1-PROPANONE

Common Name

English

IBUDILAST [MI]

Common Name

English

MN-166

Code

English

IBUDILAST [JAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QR03DC04