EDARAVONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H10N2O
Molecular Weight	174.1996
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1cc(n(-c2ccccc2)n1)O

InChI

InChIKey=PLVBQEFRONZLHO-UHFFFAOYSA-N

InChI=1S/C10H10N2O/c1-8-7-10(13)12(11-8)9-5-3-2-4-6-9/h2-7,13H,1H3

HIDE SMILES / InChI

Description
Sources: http://www.mt-pharma.co.jp/e/release/nr/2016/pdf/e_MTPC160620_RC.pdf

Edaravone is a free radical scavenger developed for the treatment of amyotrophic lateral sclerosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Target ID: CHEMBL1689064: Hydroxyl Radical Sources: http://www.e-search.ne.jp/~jpr/PDF/MT18.PDF	Binding Agent 996

Conditions

Condition	Modality	Targets	Highest Phase	Product
Amyotrophic lateral sclerosis 39 Sources: http://www.mt-pharma.co.jp/e/release/nr/2016/pdf/e_MTPC160620_RC.pdf	Primary		Approved 8043	RADICUT Approved Use Improvement of neurological symptoms, disorder of activities of daily living, and functional disorder associated with acute ischaemic stroke; Inhibition on progression of functional disorder in patients with amyotrophic lateral sclerosis (ALS). Launch Date 1.26342726E12
Acute ischemic stroke 19 Sources: http://www.mt-pharma.co.jp/e/release/nr/2016/pdf/e_MTPC160620_RC.pdf	Primary		Approved 8043	RADICUT Approved Use Improvement of neurological symptoms, disorder of activities of daily living, and functional disorder associated with acute ischaemic stroke; Inhibition on progression of functional disorder in patients with amyotrophic lateral sclerosis (ALS). Launch Date 1.26342726E12

C_max

Value	Dose	Analyte	Population
2.48 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22762844/	30 mg 2 times / day multiple, intravenous dose: 30 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2030.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, sublingual dose: 30 mg route of administration: Sublingual experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2354 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1049.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28872908/	60 mg 1 times / day multiple, intravenous dose: 60 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
5.24 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22762844/	30 mg 2 times / day multiple, intravenous dose: 30 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5576.72 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, sublingual dose: 30 mg route of administration: Sublingual experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5981.91 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1373.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28872908/	60 mg 1 times / day multiple, intravenous dose: 60 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22762844/	30 mg 2 times / day multiple, intravenous dose: 30 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.83 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, sublingual dose: 30 mg route of administration: Sublingual experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.04 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30241688/	30 mg single, intravenous dose: 30 mg route of administration: Intravenous experiment type: SINGLE co-administered:	EDARAVONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.86 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28872908/	60 mg 1 times / day multiple, intravenous dose: 60 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:	EDARAVONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg 1 times / day multiple, intravenous Recommended Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77	unhealthy, 58.8 years (range: 29 - 75 years) n = 184 Health Status: unhealthy Age Group: 58.8 years (range: 29 - 75 years) Sex: M+F Population Size: 184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77	Disc. AE: Respiratory disorder, Respiratory failure... AEs leading to discontinuation/dose reduction: Respiratory disorder (0.5%) Respiratory failure (1.1%) Toxic skin eruption (0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77

AEs

AE	Significance	Dose	Population
Respiratory disorder	0.5% Disc. AE	60 mg 1 times / day multiple, intravenous Recommended Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77	unhealthy, 58.8 years (range: 29 - 75 years) n = 184 Health Status: unhealthy Age Group: 58.8 years (range: 29 - 75 years) Sex: M+F Population Size: 184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77
Toxic skin eruption	0.5% Disc. AE	60 mg 1 times / day multiple, intravenous Recommended Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77	unhealthy, 58.8 years (range: 29 - 75 years) n = 184 Health Status: unhealthy Age Group: 58.8 years (range: 29 - 75 years) Sex: M+F Population Size: 184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77
Respiratory failure	1.1% Disc. AE	60 mg 1 times / day multiple, intravenous Recommended Dose: 60 mg, 1 times / day Route: intravenous Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77	unhealthy, 58.8 years (range: 29 - 75 years) n = 184 Health Status: unhealthy Age Group: 58.8 years (range: 29 - 75 years) Sex: M+F Population Size: 184 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000MedR.pdf Page: p. 77

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1467 inducer 707	inhibitor 1604	inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2B6 717 CYP2C8 818 CYP2C19 1325 UGT1A1 192 UGT2B7 141 P-gp 1330 BCRP 643 OATP1B1 733 OATP1B3 657 OAT1 554 OAT3 588 OCT2 594		CYP1A2 637 CYP2B6 501

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1532	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2B6 884	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2B6 884	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2C8 865	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP3A4 1772	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4 1772	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OAT1 558	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OATP1B1 748	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OATP1B3 666	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OCT2 595	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
P-gp 1514	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
UGT1A1 240	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
UGT2B7 152	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
BCRP 713	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 121 uM]
OAT1 558	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 13.6 uM]	edaravone sulfate 1
OAT3 590	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 2.74 uM]	edaravone sulfate 1
OAT3 590	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 72.3 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 84.5 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000PharmR.pdf#page=8 Page: 8.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31530	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31530
ChemicalBook	CB02130134	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02130134
ChemicalBook	CB1287462	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1287462
MolPort	MolPort-000-182-197	https://www.molport.com/shop/molecule-link/MolPort-000-182-197
Selleck Chemicals	Edaravone	http://www.selleckchem.com/products/Edaravone.html
ZINC	ZINC000018203737	http://zinc15.docking.org/substances/ZINC000018203737
eMolecules	529123	https://www.emolecules.com/cgi-bin/more?vid=529123

PubMed

Title	Date	PubMed
Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats.	2002 Sep 13	12231392
A free radical scavenger, edaravone, attenuates steatosis and cell death via reducing inflammatory cytokine production in rat acute liver injury.	2003 Aug	14567445
Normalization by edaravone, a free radical scavenger, of irradiation-reduced endothelial nitric oxide synthase expression.	2003 Aug 22	12969758
Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig.	2003 Mar 7	12600698
Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin.	2003 Oct	12954792
Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats.	2004 Jan	14654979
Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney.	2004 May	15086910
Edaravone protects against lung injury induced by intestinal ischemia/reperfusion in rat.	2005 Feb 1	15629865
Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats.	2005 Jan	15629513
MCI-186 (edaravone), a free radical scavenger, attenuates hepatic warm ischemia-reperfusion injury in rats.	2005 Jul	15948865
Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase.	2005 Mar	15721014
The antioxidant edaravone attenuates pressure overload-induced left ventricular hypertrophy.	2005 May	15824197
Clinical analysis of 207 patients who developed renal disorders during or after treatment with edaravone reported during post-marketing surveillance.	2007 Dec	18085390
Edaravone reduces ischemia-reperfusion injury mediators in rat liver.	2007 Jan	17064733
Edaravone inhibits the induction of iNOS gene expression at transcriptional and posttranscriptional steps in murine macrophages.	2008 Dec	18496239
Administration of free radical scavenger edaravone associated with higher frequency of hemorrhagic transformation in patients with cardiogenic embolism.	2008 Jul	18654047
The radical scavenger edaravone counteracts diabetes in multiple low-dose streptozotocin-treated mice.	2008 Mar 31	18291360
Edaravone protects against MPP+ -induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway.	2008 Sep	18643790
[Effects of edaravone on the expression of interleukin-1beta, nuclear factor-kappaB and neuron apoptosis in juvenile rat hippocampus after status convulsion].	2009 Aug	19951488
Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator.	2009 Feb	19095969
Expression of syndecan-2 in the amoeboid microglial cells and its involvement in inflammation in the hypoxic developing brain.	2009 Feb	18803305
Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus.	2009 Jan	18672383
Protective effect of edaravone against tobramycin-induced ototoxicity.	2009 Jan	18607936
Protective effect of edaravone against PrP106-126-induced PC12 cell death.	2010 Jul-Aug	20806394
Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation.	2010 Mar	19954754
Protective effect of edaravone, a free-radical scavenger, on ischaemia-reperfusion injury in the rat testis.	2010 Mar	19694712
Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury.	2010 Mar 25	20035747
[Effects of edaravone on the expression of GRP78, Caspase-12, and neuron apoptosis in juvenile rat hippocampus after status convulsive].	2011 Jan	21429313
Edaravone, a novel antidote against lung injury and pulmonary fibrosis induced by paraquat?	2011 Jan	21040696
A novel pyrazolone-based derivative induces apoptosis in human esophageal cells via reactive oxygen species (ROS) generation and caspase-dependent mitochondria-mediated pathway.	2015 Apr 25	25684395
Change in soluble epoxide hydrolase (sEH) during cisplatin-induced acute renal failure in mice.	2015 Aug	26165641

Patents

Sample Use Guides

In Vivo Use Guide

30 mg of edaravone diluted with an appropriate volume of physiological saline, intravenously over 30 minutes twice a day in the morning and the evening (stroke); 60 mg of edaravone diluted with an appropriate volume of physiological saline, intravenously over 60 minutes once a day (amyotrophic lateral sclerosis).

Route of Administration: Intravenous

In Vitro Use Guide

1 uM or more of edaravone inhibited cultured vascular endothelial cell injury in vitro caused by 15-HPETE (hydroperoxyeicosatetraenoic acid).

Name

Type

Language

EDARAVONE

Official Name

English

3H-PYRAZOL-3-ONE, 2,4-DIHYDRO-5-METHYL-2-PHENYL-

Systematic Name

English

COLOREX PMP

Brand Name

English

ANTIPYRINE RELATED COMPOUND A

Common Name

English

NORPHENAZONE [MI]

Common Name

English

NSC-12

Code

English

NSC-2629

Code

English

C.I. DEVELOPER 1

Common Name

English

NORPHENAZONE

Common Name

English

DEVELOPER Z

Common Name

English

RADICUT

Brand Name

English

EDARAVONE [USAN]

Common Name

English

EDARAVONE [HSDB]

Common Name

English

EDARAVONE [WHO-DD]

Common Name

English

MCI-186

Code

English

1-PHENYL-3-METHYL-5-PYRAZOLONE

Systematic Name

English

EDARAVONE [ORANGE BOOK]

Common Name

English

RADICAVA

Brand Name

English

NSC-26139

Code

English

JAROCOL PMP

Brand Name

English

3-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONE

Systematic Name

English

PHENYL METHYL PYRAZOLONE

Official Name

English

ANTIPYRINE RELATED COMPOUND A [USP-RS]

Common Name

English

EDARAVONE [MART.]

Common Name

English

EDARAVONE [JAN]

Common Name

English

PHENYLMETHYLPYRAZOLONE

Systematic Name

English

PHENYL METHYL PYRAZOLONE [INCI]

Common Name

English

EDARAVONE [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509