Details of the Drug Combination

General Information of Drug Combination (ID: DCU6ESN)

• Drug Combination Name: Kanamycin + Fosfomycin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Kanamycin (DM2DMPO): Small molecular drug
  Fosfomycin (DMVGPMX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.13
  Bliss Independence Score: 2.13
  Loewe Additivity Score: 18.12
  LHighest Single Agent (HSA) Score: 18.12

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	[6]

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	[7]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[8]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[8]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Metabolism	[9]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Metabolism	[9]

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	[10]

Indication(s) of Fosfomycin

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[4]
Urinary tract infection	GC08	Approved	[5]

Fosfomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)	TTICX3S	MURA_ECOLI	Inhibitor	[11]

Fosfomycin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[12]

Fosfomycin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[13]

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] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [5] Fosfomycin FDA Label
• [6] 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.
• [7] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63.
• [12] Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria. Antimicrob Agents Chemother. 1988 Oct;32(10):1552-6.
• [13] [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.