Details of the Drug Combination

General Information of Drug Combination (ID: DCOGZYY)

• Drug Combination Name: Kanamycin + Artemisinin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Kanamycin (DM2DMPO): Small molecular drug
  Artemisinin (DMOY7W3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 24.87
  Bliss Independence Score: 24.87
  Loewe Additivity Score: 39.31
  LHighest Single Agent (HSA) Score: 39.35

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Kanamycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Cholangitis	N.A.	Approved	[2]
Urinary tract infection	GC08	Approved	[2]

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	[5]

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	[6]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[7]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[7]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Metabolism	[8]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Metabolism	[8]

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	[9]

Indication(s) of Artemisinin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]

Artemisinin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase)	TT3PQ2Y	PYRD_PLAF7	Inhibitor	[4]
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	TTZVSJ2	NOUNIPROTAC	Inhibitor	[4]

Artemisinin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[11]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[12]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[10]

Artemisinin Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Activity	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[13]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[13]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[14]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[14]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[13]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[15]
Isocitrate dehydrogenase subunit alpha, mitochondrial (IDH3A)	OT5QQB5L	IDH3A_HUMAN	Decreases Expression	[15]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Activity	[16]

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] Kanamycin FDA Label
• [3] Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
• [4] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [5] 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.
• [6] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [7] 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.
• [8] 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.
• [9] A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals. Toxicology. 2009 Oct 1;264(1-2):1-9. doi: 10.1016/j.tox.2009.07.021. Epub 2009 Aug 7.
• [10] Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
• [11] Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35.
• [12] Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
• [13] Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
• [14] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [15] Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
• [16] In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest. 2006 Sep;36(9):647-53. doi: 10.1111/j.1365-2362.2006.01700.x.