Details of the Drug Combination

General Information of Drug Combination (ID: DCEYDUA)

• Drug Combination Name: Ramelteon + Enoxacin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ramelteon (DM7IW9J): Small molecular drug
  Enoxacin (DMYTE6L): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.24
  Bliss Independence Score: 3.24
  Loewe Additivity Score: 18.17
  LHighest Single Agent (HSA) Score: 18.17

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ramelteon

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[2]
Circadian rhythm sleep disorder	7A60-7A65	Terminated	[2]

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	[6]
Melatonin receptor type 1A (MTNR1A)	TT0WAIE	MTR1A_HUMAN	Modulator	[6]

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	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

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	[5]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[5]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Decreases Expression	[5]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[5]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Decreases Expression	[5]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Increases Expression	[5]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Decreases Expression	[5]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[5]

Indication(s) of Enoxacin

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[3]
Urinary tract infection	GC08	Approved	[4]

Enoxacin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Inhibitor	[9]

Enoxacin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[11]

Enoxacin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Affects Binding	[13]

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] 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).
• [3] Enoxacin FDA Label
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019616.
• [5] 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.
• [6] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [7] 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.
• [8] Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.
• [9] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [10] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones. J Pharmacol Exp Ther. 2009 Feb;328(2):628-34.
• [11] Identification of influx transporter for the quinolone antibacterial agent levofloxacin. Mol Pharm. 2007 Jan-Feb;4(1):85-94.
• [12] Interaction study between enoxacin and fluvoxamine. Ther Drug Monit. 2005 Jun;27(3):349-53.
• [13] Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG. Toxicology. 2021 Jun 30;458:152822. doi: 10.1016/j.tox.2021.152822. Epub 2021 May 28.