Details of the Drug

General Information of Drug (ID: DM8ZHP1)

Drug Name
MCI-186
Synonyms
Edarabone; Edaravone; Methylphenylpyrazolone; Monopyrazolone; Norantipyrine; Norphenazone; Phenylmethylpyrazolone; Radicut; Developer Z; Edaravone [INN]; Phenyl methyl pyrazolone; CDS1_000986; CI Developer 1; IN1263; M0687; MCI 186; Edaravone(jan); Radicut (TN); AE-641/00371017; C.I. Developer 1; Edaravone (JAN/INN); (MCI-186); 1-Fenyl-3-methyl-2-pyrazolin-5-on; 1-Fenyl-3-methyl-2-pyrazolin-5-on [Czech]; 1-Phenyl-3-methyl-5-oxo-2-pyrazoline; 1-Phenyl-3-methyl-5-pyrazolone; 1-Phenyl-3-methylpyrazolone; 1-Phenyl-3-methylpyrazolone-5; 2,4-Dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one; 3-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONE; 3-Methyl-1-phenyl-2-pyrazoline-5-one; 3-Methyl-1-phenyl-5-pyrazolone; 3-Methyl-1-phenylpyrazol-5-one; 5-Methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one; 5-methyl-2-phenyl-4H-pyrazol-3-one
Indication
Disease Entry ICD 11 Status REF
Amyotrophic lateral sclerosis 8B60.0 Approved [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 174.2
Logarithm of the Partition Coefficient (xlogp) 1.3
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 2.95 mgh/L [2]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 263 mcg/L [2]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2.3 h [2]
Clearance
The clearance of drug is 0.1 L/min [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 4.5 - 6 hours [4]
Metabolism
The drug is metabolized via renal []
Vd
The volume of distribution (Vd) of drug is 18.5 L/kg [3]
Chemical Identifiers
Formula
C10H10N2O
IUPAC Name
5-methyl-2-phenyl-4H-pyrazol-3-one
Canonical SMILES
CC1=NN(C(=O)C1)C2=CC=CC=C2
InChI
InChI=1S/C10H10N2O/c1-8-7-10(13)12(11-8)9-5-3-2-4-6-9/h2-6H,7H2,1H3
InChIKey
QELUYTUMUWHWMC-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4021
ChEBI ID
CHEBI:31530
CAS Number
89-25-8
DrugBank ID
DB12243
TTD ID
D06DLI
VARIDT ID
DR00101
INTEDE ID
DR1756
ACDINA ID
D01030
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Regulator (upregulator) [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [6]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)
Main DME 		DEYGVN4 UD11_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Beta-nerve growth factor (NGF) OTOLABJT NGF_HUMAN Gene/Protein Processing [8]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [9]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Gene/Protein Processing [9]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Gene/Protein Processing [9]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Gene/Protein Processing [10]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Post-Translational Modifications [8]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Protein Interaction/Cellular Processes [11]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Amyotrophic lateral sclerosis
ICD Disease Classification 8B60.0
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Apoptosis regulator Bcl-2 (BCL-2) DTT BCL2 2.52E-02 0.17 0.72
Organic anion transporter 3 (SLC22A8) DTP OAT3 8.95E-02 -1.21E-01 -4.10E-01
Organic anion transporter 3 (SLC22A8) DTP OAT3 5.50E-01 4.15E-02 1.96E-01
Organic anion transporter 1 (SLC22A6) DTP OAT1 5.80E-01 4.39E-02 1.78E-01
Organic anion transporter 1 (SLC22A6) DTP OAT1 4.64E-01 -3.69E-02 -2.34E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 6.40E-01 3.70E-02 1.48E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 5.01E-01 1.93E-01 4.52E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Cysteine hydrochloride E00318 25150 Antioxidant
Phosphoric acid E00039 1004 Acidulant; Buffering agent
Sodium chloride E00077 5234 Diluent; Tonicity agent
Sodium hydroxide E00234 14798 Alkalizing agent
Sodium sulhydrate E00549 23665763 Antimicrobial preservative
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Edaravone 30 mg/100 ml Injection 30 mg/100 ml Injection Intravenous
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
2 Pharmacokinetics and clinical pharmacology of indapamide. Am Heart J. 1983 Jul;106(1 Pt 2):212-20. doi: 10.1016/0002-8703(83)90119-9.
3 Li H, Xu K, Wang Y, Zhang H, Li T, Meng L, Gong X, Zhang H, Ou N, Ruan J: Phase I clinical study of edaravone in healthy Chinese volunteers: safety and pharmacokinetics of single or multiple intravenous infusions. Drugs R D. 2012 Jun 1;12(2):65-70. doi: 10.2165/11634290-000000000-00000.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
6 Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate. Drug Metab Dispos. 2007 Aug;35(8):1429-34.
7 A novel administration route for edaravone: I. Effects of metabolic inhibitors on skin permeability of edaravone. Int J Pharm. 2009 May 8;372(1-2):33-8.
8 Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation. Neurosci Res. 2010 Mar;66(3):284-9. doi: 10.1016/j.neures.2009.11.011. Epub 2009 Nov 30.
9 A novel pyrazolone-based derivative induces apoptosis in human esophageal cells via reactive oxygen species (ROS) generation and caspase-dependent mitochondria-mediated pathway. Chem Biol Interact. 2015 Apr 25;231:1-9. doi: 10.1016/j.cbi.2015.02.004. Epub 2015 Feb 13.
10 Edaravone inhibits rheumatoid synovial cell proliferation and migration. Free Radic Res. 2006 Feb;40(2):121-5. doi: 10.1080/10715760500401116.
11 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. Atherosclerosis. 2005 Mar;179(1):97-102. doi: 10.1016/j.atherosclerosis.2004.10.037. Epub 2004 Dec 19.