EDARAVONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H10N2O
Molecular Weight	174.1992
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NN(C(=O)C1)C2=CC=CC=C2

InChI

InChIKey=QELUYTUMUWHWMC-UHFFFAOYSA-N

InChI=1S/C10H10N2O/c1-8-7-10(13)12(11-8)9-5-3-2-4-6-9/h2-6H,7H2,1H3

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
CHEMBL1689064: Hydroxyl Radical 1 Target ID: CHEMBL1689064: Hydroxyl Radical Sources: http://www.e-search.ne.jp/~jpr/PDF/MT18.PDF	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Amyotrophic lateral sclerosis 41 Sources: http://www.mt-pharma.co.jp/e/release/nr/2016/pdf/e_MTPC160620_RC.pdf	Primary		Approved 8429	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 2010
Acute ischemic stroke 19 Sources: http://www.mt-pharma.co.jp/e/release/nr/2016/pdf/e_MTPC160620_RC.pdf	Primary		Approved 8429	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 2010

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 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 UGT1A1 204 UGT2B7 146 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647		CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 121 uM]
OAT1 603	inhibitor 3277 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 644	inhibitor 3277 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 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209176Orig1s000ClinPharmR.pdf#page=41 Page: 41.0	yes [IC50 72.3 uM]
CYP2C9 1819	inhibitor 3277 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 1647	inhibitor 1626 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
Clinical usefulness of edaravone for acute liver injury.	2003 Jul	12795759
A novel free radical scavenger, edarabone, protects against cisplatin-induced acute renal damage in vitro and in vivo.	2003 Jun	12649298
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
The antioxidant edaravone attenuates pressure overload-induced left ventricular hypertrophy.	2005 May	15824197
Edaravone inhibits rheumatoid synovial cell proliferation and migration.	2006 Feb	16390820
An antioxidant treatment potentially protects myocardial energy metabolism by regulating uncoupling protein 2 expression in a chronic beta-adrenergic stimulation rat model.	2006 May 15	16580698
Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats.	2007 Dec	18031376
Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia.	2007 Dec	17889387
Edaravone reduces ischemia-reperfusion injury mediators in rat liver.	2007 Jan	17064733
[Ischemic stroke associated with LH-RH analogue (leuprorelin) administration in a young woman].	2007 May	17585607
Administration of free radical scavenger edaravone associated with higher frequency of hemorrhagic transformation in patients with cardiogenic embolism.	2008 Jul	18654047
Edaravone prevents iNOS expression by inhibiting its promoter transactivation and mRNA stability in cytokine-stimulated hepatocytes.	2008 Mar	18078833
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
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
Expression of angiotensin II and its receptors in the normal and hypoxic amoeboid microglial cells and murine BV-2 cells.	2009 Feb 18	19118600
Protective effect of edaravone against tobramycin-induced ototoxicity.	2009 Jan	18607936
Reactive oxygen species modulate growth of cerebral aneurysms: a study using the free radical scavenger edaravone and p47phox(-/-) mice.	2009 Jul	19381132
[Effects of edaravone on IRE1 mRNA expression and neuronal apoptosis in the hippocampus of rats with status convulsivus].	2009 Jun	19558813
Oxygen-glucose deprivation activates 5-lipoxygenase mediated by oxidative stress through the p38 mitogen-activated protein kinase pathway in PC12 cells.	2009 Mar	18951527
Protective effect of edaravone against PrP106-126-induced PC12 cell death.	2010 Jul-Aug	20806394
Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury.	2010 Mar 25	20035747
Edaravone, a novel antidote against lung injury and pulmonary fibrosis induced by paraquat?	2011 Jan	21040696
Edaravone inhibits hypoxia-induced trophoblast-soluble Fms-like tyrosine kinase 1 expression: a possible therapeutic approach to preeclampsia.	2014 Jul	24840734
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
Ginsenoside Rd attenuates Aβ25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons.	2015 Sep 5	26111763

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

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

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

PHENAZONE IMPURITY A [EP IMPURITY]

Common Name

English

Edaravone [WHO-DD]

Common 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

ANTIPYRINE RELATED COMPOUND A [USP IMPURITY]

Common Name

English

edaravone [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1509