Details of the Drug Combination

General Information of Drug Combination (ID: DCIQWDU)

Drug Combination Name
Loperamide Ramelteon
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Loperamide   DMOJZQ9 Ramelteon   DM7IW9J
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 2.82
Bliss Independence Score: 2.82
Loewe Additivity Score: 16.67
LHighest Single Agent (HSA) Score: 16.68

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Loperamide
Disease Entry ICD 11 Status REF
Diarrhea ME05.1 Approved [2]
Traveler's diarrhea ME05.1 Approved [3]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [4]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [4]
Loperamide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor delta (OPRD1) TT27RFC OPRD_HUMAN Binder [6]
------------------------------------------------------------------------------------
Loperamide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Loperamide Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [9]
Oxygen-insensitive NADPH nitroreductase A (nfsA) DEDPI65 NFSA_ECOLI Metabolism [10]
------------------------------------------------------------------------------------
Indication(s) of Ramelteon
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [5]
Circadian rhythm sleep disorder 7A60-7A65 Terminated [5]
Ramelteon Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Melatonin receptor type 1B (MTNR1B) TT32JK8 MTR1B_HUMAN Modulator [12]
Melatonin receptor type 1A (MTNR1A) TT0WAIE MTR1A_HUMAN Modulator [12]
------------------------------------------------------------------------------------
Ramelteon Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [14]
------------------------------------------------------------------------------------
Ramelteon Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [11]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [11]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Decreases Expression [11]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [11]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Decreases Expression [11]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Increases Expression [11]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Decreases Expression [11]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Loperamide FDA Label
4 Screening of an FDA-approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84.
5 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: 1356).
6 Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8.
7 In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab Dispos. 2008 Feb;36(2):268-75.
8 Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8.
9 Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81.
10 Reduction of the prodrug loperamide oxide to its active drug loperamide in the gut of rats, dogs, and humans. Drug Metab Dispos. 1995 Mar;23(3):354-62.
11 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
12 MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
13 Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91.
14 Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.