Details of the Drug Combination

General Information of Drug Combination (ID: DCZH6RB)

• Drug Combination Name: Carvedilol + Mefloquine
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Carvedilol (DMHTEAO): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 0.695
  Bliss Independence Score: 0.739
  Loewe Additivity Score: 0.389
  LHighest Single Agent (HSA) Score: 3.049

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Carvedilol

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[2]
Congestive heart failure	BD10	Approved	[3]
Pulmonary hypertension	BB01	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]

Carvedilol Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUAMN alpha-1 adrenergic receptor (ADRA1)	TTDBOI7	ADA1A_HUMAN; ADA1B_HUMAN; ADA1D_HUMAN	Inhibitor	[10]
Adrenergic receptor Alpha-1 (ADRA1)	TTG28O6	NOUNIPROTAC	Antagonist	[11]
HUMAN beta adrenergic receptor (BAR)	TTJB8UY	ADRB1_HUMAN; ADRB2_HUMAN; ADRB3_HUMAN	Antagonist	[4]

Carvedilol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Carvedilol Interacts with 7 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	[14]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[16]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[17]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[18]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[15]

Carvedilol Interacts with 28 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Glucuronidation	[19]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[20]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Increases Activity	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[22]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Phosphorylation	[23]
Potassium channel subfamily K member 3 (KCNK3)	OTWMAV6G	KCNK3_HUMAN	Decreases Activity	[24]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Expression	[25]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[26]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[27]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[28]
Vasopressin-neurophysin 2-copeptin (AVP)	OTAVZ76K	NEU2_HUMAN	Decreases Expression	[29]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[30]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[31]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[32]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[33]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Phosphorylation	[22]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[27]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Affects Activity	[34]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Decreases Expression	[35]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Increases Expression	[36]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Expression	[37]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[22]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[38]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Decreases Expression	[35]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[32]
Ryanodine receptor 2 (RYR2)	OT0PF19E	RYR2_HUMAN	Increases Activity	[39]
Vascular endothelial growth factor receptor 2 (KDR)	OT15797V	VGFR2_HUMAN	Increases ADR	[40]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Increases ADR	[40]

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[7]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[7]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[8]

Mefloquine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium 80S ribosome (Malaria 80S)	TTT28H3	NOUNIPROTAC	Binder	[41]

Mefloquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[42]

Mefloquine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[43]

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