Details of the Drug Combination

General Information of Drug Combination (ID: DCWQU6X)

• Drug Combination Name: Tacrine + Kanamycin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Tacrine (DM51FY6): Small molecular drug
  Kanamycin (DM2DMPO): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.87
  Bliss Independence Score: 6.87
  Loewe Additivity Score: 19.77
  LHighest Single Agent (HSA) Score: 19.77

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	[5]

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	[6]

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	[7]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[8]

Tacrine Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[9]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[10]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Decreases Activity	[11]
Ribosyldihydronicotinamide dehydrogenase (NQO2)	OTGDAJRZ	NQO2_HUMAN	Decreases Activity	[11]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[12]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[13]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Decreases Activity	[14]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[16]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases ADR	[17]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[18]

Indication(s) of Kanamycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[3]
Bacterial infection	1A00-1C4Z	Approved	[4]
Cholangitis	N.A.	Approved	[3]
Urinary tract infection	GC08	Approved	[3]

Kanamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[19]

Kanamycin Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[20]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[21]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[21]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Metabolism	[22]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Metabolism	[22]

Kanamycin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Increases Expression	[23]

References

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• [3] Kanamycin FDA Label
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• [15] High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
• [16] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
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• [18] Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos. 2011 Aug;39(8):1388-95. doi: 10.1124/dmd.110.037077. Epub 2011 May 3.
• [19] SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli. Genes Cells. 2002 Jul;7(7):629-38.
• [20] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [21] Cloning and expression of novel aminoglycoside phosphotransferase genes from Campylobacter and their role in the resistance to six aminoglycosides. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: e01682-17.
• [22] Expression of Clostridium thermocellum endoglucanase gene in Lactobacillus gasseri and Lactobacillus johnsonii and characterization of the genetically modified probiotic lactobacilli. Curr Microbiol. 2000 Apr;40(4):257-63.
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