Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM8ZHP1)

Drug Name
MCI-186 Drug Info
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]
Cross-matching ID
PubChem CID
4021
ChEBI ID
CHEMBL31530
CAS Number
CAS 89-25-8
TTD Drug ID
DM8ZHP1
VARIDT Drug ID
DR00101
INTEDE Drug ID
DR1756
ACDINA Drug ID
D01030

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DME
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Apoptosis regulator Bcl-2 (BCL-2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Taxol DMUOT9V Breast cancer 2C60-2C65 Approved [7]
GDC-0199 DMH0QKA Chronic lymphocytic leukaemia 2A82.0 Approved [8]
ABT-263 DMNE56X Myelofibrosis 2A20.2 Phase 3 [9]
Taxol/Paraplatin/Herceptin DML6GAN Breast cancer 2C60-2C65 Phase 3 [10]
Oblimersen DM7KI4E Melanoma 2C30 Phase 3 [11]
RG7601 DMDVAFP Chronic lymphocytic leukaemia 2A82.0 Phase 3 [8]
Thymoquinone DMVDTR2 Polycystic ovarian syndrome 5A80.1 Phase 2/3 [12]
Obatoclax DMPF9ZM Solid tumour/cancer 2A00-2F9Z Phase 2 [13]
PI-88/Taxotere DM4FIWC Solid tumour/cancer 2A00-2F9Z Phase 2 [14]
Gossypol DMJWE3I Prostate cancer 2C82.0 Phase 2 [15]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic anion transporter 1 (SLC22A6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Amoxicillin DMUYNEI Acute otitis media AB00 Approved [16]
Methotrexate DM2TEOL Anterior urethra cancer Approved [17]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [18]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [19]
Aciclovir DMYLOVR Genital herpes 1A94 Approved [19]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [19]
Cefazolin DMPDYFR Bacteremia 1A73 Approved [20]
Olmesartan medoxomil DMWBHRY High blood pressure BA00 Approved [21]
Zalcitabine DMH7MUV Human immunodeficiency virus infection 1C62 Approved [22]
FLUORESCEIN DMQTFAO Ocular disease 1F00.1Z Approved [23]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic anion transporter 3 (SLC22A8)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL Anterior urethra cancer Approved [24]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [18]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [19]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [25]
Pravastatin DM6A0X7 Adult acute monocytic leukemia Approved [26]
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [27]
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [28]
PITAVASTATIN CALCIUM DM1UJO0 Dyslipidemia 5C80-5C81 Approved [29]
Rosuvastatin DMMIQ7G Arteriosclerosis BD40 Approved [30]
Cilostazol DMZMSCT Intermittent claudication BD40.00 Approved [31]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [32]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [33]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [34]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [35]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [36]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [37]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [38]
Metronidazole DMTIVEN Abscess Approved [39]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [40]
Ethanol DMDRQZU Chronic pain MG30 Approved [41]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Poly polymerase 1 (PARP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [42]
Gefitinib DM15F0X Colon adenocarcinoma Approved [43]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [44]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [45]
Citalopram DM2G9AE Acute coronary syndrome BA41 Approved [46]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [47]
Imipramine DM2NUH3 Depression 6A70-6A7Z Approved [46]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [48]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [49]
Methotrexate DM2TEOL Anterior urethra cancer Approved [50]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Mitogen-activated protein kinase 8 (MAPK8)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [51]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [52]
Gefitinib DM15F0X Colon adenocarcinoma Approved [53]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [54]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [55]
Quercetin DM3NC4M Obesity 5B81 Approved [56]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [57]
Glucosamine DM4ZLFD Osteoarthritis FA00-FA05 Approved [58]
Vinblastine DM5TVS3 Advanced cancer 2A00-2F9Z Approved [55]
Ethacrynic acid DM60QMR Edema MG29 Approved [59]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

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

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

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME DEYGVN4 UD11_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Post-Translational Modifications [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [6]

References

1 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
2 Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
3 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.
4 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.
5 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.
6 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.
7 Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
8 ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.
9 Clinical pipeline report, company report or official report of Roche (2009).
10 Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32.
11 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
12 Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197.
13 Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9.
14 Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer. Ann Oncol. 2010 Jun;21(6):1302-7.
15 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
16 The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9.
17 Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9.
18 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
19 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
20 Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
21 Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
22 Interaction of zalcitabine with human organic anion transporter 1. Pharmazie. 2006 May;61(5):491-2.
23 Apical expression or expression in a non polarized cell of hOAT1 inverses regulation by epidermal growth factor (EGF) as compared to basolateral hOAT1. Cell Physiol Biochem. 2004;14(3):177-86.
24 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
25 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
26 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
27 Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
28 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
29 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
30 The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
31 Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
32 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
33 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
34 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
35 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
36 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
37 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
38 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
39 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
40 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
41 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
42 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
43 Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
44 Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
45 Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
46 The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
47 Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
48 Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
49 Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
50 Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
51 Cisplatin induces autophagy to enhance hepatitis B virus replication via activation of ROS/JNK and inhibition of the Akt/mTOR pathway. Free Radic Biol Med. 2019 Feb 1;131:225-236. doi: 10.1016/j.freeradbiomed.2018.12.008. Epub 2018 Dec 11.
52 Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures. Sci Rep. 2020 Feb 14;10(1):2687. doi: 10.1038/s41598-020-59468-4.
53 Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways. World J Gastrointest Oncol. 2022 Feb 15;14(2):450-477. doi: 10.4251/wjgo.v14.i2.450.
54 Neuroprotective effects of glucomoringin-isothiocyanate against H(2)O(2)-Induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. Neurotoxicology. 2019 Dec;75:89-104. doi: 10.1016/j.neuro.2019.09.008. Epub 2019 Sep 12.
55 Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces apoptosis in human colon carcinoma HCT116 cells. J Biol Chem. 2002 Nov 15;277(46):43648-58. doi: 10.1074/jbc.M203214200. Epub 2002 Sep 6.
56 Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
57 Lon protease and eiF2 are involved in acute, but not prolonged, antiretroviral induced stress response in HepG2 cells. Chem Biol Interact. 2016 May 25;252:82-6. doi: 10.1016/j.cbi.2016.03.021. Epub 2016 Apr 1.
58 Disease-modifying effects of glucosamine HCl involving regulation of metalloproteinases and chemokines activated by interleukin-1beta in human primary synovial fibroblasts. J Cell Biochem. 2008 May 1;104(1):38-50. doi: 10.1002/jcb.21597.
59 Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine. Cancer Sci. 2003 Oct;94(10):886-93.