Details of the Drug Combination

General Information of Drug Combination (ID: DCPW3LF)

• Drug Combination Name: Ramelteon + Epinephrine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ramelteon (DM7IW9J): Small molecular drug
  Epinephrine (DM3KJBC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 5.03
  Bliss Independence Score: 5.03
  Loewe Additivity Score: 6.47
  LHighest Single Agent (HSA) Score: 6.47

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 Epinephrine

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[3]
Allergy	4A80-4A85	Approved	[4]
Anaphylaxis	N.A.	Approved	[3]
Bronchiectasis	CA24	Approved	[3]
Bronchitis	CA20	Approved	[3]
Periodontitis	DA0C	Approved	[3]
Pulmonary emphysema	CA21.Z	Approved	[3]
Severe asthma	CA23	Approved	[3]
Asthma	CA23	Investigative	[3]

Epinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[9]

Epinephrine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]

Epinephrine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[12]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[13]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[14]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[15]
Monoamine oxidase type A (MAO-A)	DERE4TU	AOFA_HUMAN	Metabolism	[16]

Epinephrine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[17]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[18]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[19]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[19]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Increases Expression	[20]
Integrin alpha-V (ITGAV)	OTAM7JTR	ITAV_HUMAN	Increases Expression	[20]
Cathepsin K (CTSK)	OTT3YX5O	CATK_HUMAN	Increases Expression	[20]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[21]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[22]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[23]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Cleavage	[24]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[24]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[24]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[24]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[25]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[26]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[25]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[25]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[26]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Increases Expression	[24]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases Phosphorylation	[27]
Hormone-sensitive lipase (LIPE)	OTMMVJ8A	LIPS_HUMAN	Increases Activity	[28]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[24]
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Decreases Activity	[29]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[30]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[31]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[32]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases ADR	[30]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[33]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases ADR	[30]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[18]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[30]

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