Details of the Drug Combination

General Information of Drug Combination (ID: DCJMC4P)

• Drug Combination Name: Tacrine + Emetine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tacrine (DM51FY6): Small molecular drug
  Emetine (DMCT2YF): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.01
  Bliss Independence Score: 8.01
  Loewe Additivity Score: 10.11
  LHighest Single Agent (HSA) Score: 10.12

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tacrine

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Approved	[2]

Tacrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[4]

Tacrine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Tacrine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[7]

Tacrine Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[8]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[9]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Decreases Activity	[10]
Ribosyldihydronicotinamide dehydrogenase (NQO2)	OTGDAJRZ	NQO2_HUMAN	Decreases Activity	[10]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[11]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[12]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Decreases Activity	[13]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[14]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[15]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases ADR	[16]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[17]

Indication(s) of Emetine

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Approved	[3]

Emetine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]

Emetine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[20]

Emetine Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)	OT9QIHEQ	RECK_HUMAN	Decreases Expression	[21]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[22]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Increases Degradation	[23]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[21]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Decreases Expression	[18]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[24]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[18]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[18]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[25]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Decreases Expression	[18]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[18]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[18]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[21]

References

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• [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: 6687).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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