Details of the Drug Combination

General Information of Drug Combination (ID: DCO96RQ)

• Drug Combination Name: Spironolactone + Kanamycin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Spironolactone (DM2AQ5N): Small molecular drug
  Kanamycin (DM2DMPO): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 10.33
  Bliss Independence Score: 10.33
  Loewe Additivity Score: 23.44
  LHighest Single Agent (HSA) Score: 23.44

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Spironolactone

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[2]
Congestive heart failure	BD10	Approved	[3]
Edema	MG29	Approved	[2]
Hyperaldosteronism	5A72	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]

Spironolactone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mineralocorticoid receptor (MR)	TT26PHO	MCR_HUMAN	Modulator	[7]

Spironolactone Interacts with 21 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[8]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[9]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[10]
Serine/threonine-protein kinase Sgk1 (SGK1)	OT301T1U	SGK1_HUMAN	Increases Expression	[11]
Tissue-type plasminogen activator (PLAT)	OTQPDNAB	TPA_HUMAN	Increases Expression	[12]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[13]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[14]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[15]
Collagen alpha-1(III) chain (COL3A1)	OTT1EMLM	CO3A1_HUMAN	Decreases Expression	[14]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Increases Expression	[16]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Decreases Expression	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[17]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[18]
Myb-related protein A (MYBL1)	OTBJMC2P	MYBA_HUMAN	Increases Expression	[11]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Binding	[19]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Decreases Expression	[14]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[20]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Increases Expression	[11]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Response To Substance	[21]
Serum paraoxonase/lactonase 3 (PON3)	OT80W9TA	PON3_HUMAN	Increases Hydrolysis	[22]

Indication(s) of Kanamycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[5]
Bacterial infection	1A00-1C4Z	Approved	[6]
Cholangitis	N.A.	Approved	[5]
Urinary tract infection	GC08	Approved	[5]

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	[23]

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	[24]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[25]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[25]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Metabolism	[26]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Metabolism	[26]

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	[27]

References

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• [21] Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study. Hypertension. 1980 Sep-Oct;2(5):672-9. doi: 10.1161/01.hyp.2.5.672.
• [22] Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005 Jun;46(6):1239-47. doi: 10.1194/jlr.M400511-JLR200. Epub 2005 Mar 16.
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• [25] 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.
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