Details of the Drug Combination

General Information of Drug Combination (ID: DCQYRRG)

Drug Combination Name
MCI-186 Riluzole
Indication
Disease Entry Status REF
Neuromuscular Diseases Phase 2 [1]
Component Drugs MCI-186   DM8ZHP1 Riluzole   DMECBWN
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MCI-186
Disease Entry ICD 11 Status REF
Amyotrophic lateral sclerosis 8B60.0 Approved [2]
MCI-186 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Regulator (upregulator) [4]
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MCI-186 Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [5]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [5]
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MCI-186 Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [6]
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MCI-186 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [8]
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Indication(s) of Riluzole
Disease Entry ICD 11 Status REF
Amyotrophic lateral sclerosis 8B60.0 Approved [3]
Riluzole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A) TTN9VTF SCNBA_HUMAN Blocker [11]
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Riluzole Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
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Riluzole Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [14]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [15]
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Riluzole Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [16]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6) OTAFHAVI ATF6A_HUMAN Increases Expression [9]
Kallikrein-2 (KLK2) OT9RE37R KLK2_HUMAN Decreases Expression [9]
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References

1 ClinicalTrials.gov (NCT03272802) Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)
2 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2326).
4 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
5 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.
6 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.
7 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.
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 Riluzole induces AR degradation via endoplasmic reticulum stress pathway in androgen-dependent and castration-resistant prostate cancer cells. Prostate. 2019 Feb;79(2):140-150. doi: 10.1002/pros.23719. Epub 2018 Oct 2.
10 Drug discovery for Duchenne muscular dystrophy via utrophin promoter activation screening. PLoS One. 2011;6(10):e26169. doi: 10.1371/journal.pone.0026169. Epub 2011 Oct 20.
11 Secondary injury mechanisms of spinal cord trauma: a novel therapeutic approach for the management of secondary pathophysiology with the sodium channel blocker riluzole. Prog Brain Res. 2002;137:177-90.
12 Interactions between riluzole and ABCG2/BCRP transporter. Neurosci Lett. 2009 Mar 6;452(1):12-6.
13 Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3.
14 Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. J Pharmacol Exp Ther. 1997 Sep;282(3):1465-72.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.