Details of the Drug Combination

General Information of Drug Combination (ID: DCR1H8M)

• Drug Combination Name: Ornidazole + Gentamicin
• Indication: Colon Cancer; Status: Phase 3 [1]
• Component Drugs:
  Ornidazole (DM6QHDJ): Small molecular drug
  Gentamicin (DMKINJO): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ornidazole

Disease Entry	ICD 11	Status	REF
Amoebiasis	1A36	Approved	[2]

Ornidazole Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[5]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[5]
Flavin adenine dinucleotide dehydrogenase (fadd)	DE90ZBW	APBE1_KLEP3	Metabolism	[6]
Flavin adenine dinucleotide dehydrogenase (fadd)	DEXG57F	APBE1_KLEP3	Metabolism	[6]
Flavin adenine dinucleotide dehydrogenase (fadd)	DE5CJFM	APBE1_KLEP3	Metabolism	[6]
Flavin adenine dinucleotide dehydrogenase (fadd)	DE9WXYE	APBE1_KLEP3	Metabolism	[6]
Oxygen-insensitive NADPH nitroreductase A (nfsA)	DEX5D46	NFSA_SALTY	Metabolism	[7]

Indication(s) of Gentamicin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[3]
Bacterial infection	1A00-1C4Z	Approved	[4]
Blepharoconjunctivitis	N.A.	Approved	[3]
Cholangitis	N.A.	Approved	[3]
Dacryocystitis	N.A.	Approved	[3]
Demodex blepharitis	1G07	Approved	[3]
Folliculitis	N.A.	Approved	[3]
Neonatal sepsis	N.A.	Approved	[3]
Paronychia	1F23.13	Approved	[3]
Peritonitis	N.A.	Approved	[3]
Pseudomonas aeruginosa infectious disease	N.A.	Approved	[3]

Gentamicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA)	TTOVFH2	NOUNIPROTAC	Modulator	[10]

Gentamicin Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[11]
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Metabolism	[12]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Metabolism	[12]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Metabolism	[13]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Metabolism	[13]
Aminoglycoside 6'-N-acetyltransferase (aacA)	DE48UAX	C5MQW3_KLEPO	Metabolism	[14]

Gentamicin Interacts with 28 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Exocyst complex component 3 (EXOC3)	OT8N3306	EXOC3_HUMAN	Increases Expression	[15]
Slit homolog 1 protein (SLIT1)	OT35RBNT	SLIT1_HUMAN	Decreases Expression	[9]
Cystatin-C (CST3)	OTNZ6AO4	CYTC_HUMAN	Increases Expression	[15]
Methylmalonyl-CoA mutase, mitochondrial (MMUT)	OTBBBV70	MUTA_HUMAN	Affects Expression	[16]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[8]
Endothelin receptor type B (EDNRB)	OTLLZV3P	EDNRB_HUMAN	Increases Expression	[9]
Insulin-like growth factor-binding protein 5 (IGFBP5)	OTRE5V0C	IBP5_HUMAN	Decreases Expression	[9]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Increases Expression	[9]
ATP-sensitive inward rectifier potassium channel 1 (KCNJ1)	OTIXCRI6	KCNJ1_HUMAN	Increases Expression	[17]
Cytosolic purine 5'-nucleotidase (NT5C2)	OTJMF66Z	5NTC_HUMAN	Increases Expression	[9]
Potassium voltage-gated channel subfamily KQT member 4 (KCNQ4)	OT29B58J	KCNQ4_HUMAN	Decreases Expression	[9]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[15]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Expression	[18]
Polycystin-2 (PKD2)	OTIXBU8H	PKD2_HUMAN	Increases Expression	[19]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Increases Expression	[8]
Partitioning defective 3 homolog (PARD3)	OTH5BPLO	PARD3_HUMAN	Decreases Expression	[9]
GATOR1 complex protein NPRL2 (NPRL2)	OTOB10MO	NPRL2_HUMAN	Decreases Expression	[9]
Hepatitis A virus cellular receptor 1 (HAVCR1)	OT184CRZ	HAVR1_HUMAN	Increases Expression	[15]
Rho guanine nucleotide exchange factor 26 (ARHGEF26)	OTX0U8PX	ARHGQ_HUMAN	Increases Expression	[9]
Polyadenylate-binding protein-interacting protein 1 (PAIP1)	OTL2F5T5	PAIP1_HUMAN	Decreases Expression	[9]
Large subunit GTPase 1 homolog (LSG1)	OTDAXJ9L	LSG1_HUMAN	Decreases Expression	[9]
Glyoxalase domain-containing protein 4 (GLOD4)	OTBJKFXA	GLOD4_HUMAN	Decreases Expression	[9]
DNA-directed DNA/RNA polymerase mu (POLM)	OT0SRIP4	DPOLM_HUMAN	Increases Expression	[9]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)	OT28VBVK	ATG3_HUMAN	Decreases Expression	[9]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (PLCB1)	OT9HYT7A	PLCB1_HUMAN	Increases ADR	[20]
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Increases Transport	[21]
Lysosomal Pro-X carboxypeptidase (PRCP)	OTIUY91L	PCP_HUMAN	Increases ADR	[20]
Dipeptidyl aminopeptidase-like protein 6 (DPP6)	OTWW3H0K	DPP6_HUMAN	Increases ADR	[20]

References

• [1] ClinicalTrials.gov (NCT03475680) Mechanical Bowel Preparation and Oral Antibiotics Before Colon Cancer Surgery
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Gentamicin FDA Label
• [4] 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: 2427).
• [5] Effect of ketoconazole on the pharmacokinetics of ornidazole--a possible role of p-glycoprotein and CYP3A. Drug Metabol Drug Interact. 2006;22(1):67-77.
• [6] Reduction of azo dyes and nitroaromatic compounds by bacterial enzymes from the human intestinal tract. Environ Health Perspect. 1995 Jun;103 Suppl 5:17-9.
• [7] Identification and characterization of SnrA, an inducible oxygen-insensitive nitroreductase in Salmonella enterica serovar Typhimurium TA1535. Mutat Res. 2002 Oct 31;508(1-2):59-70.
• [8] A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
• [9] Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [12] 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.
• [13] 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.
• [14] Detection of multidrug-resistant Enterobacteriaceae isolated from river waters flowing to the Guanabara Bay and from clinical samples of hospitals in Rio de Janeiro, Brazil. Biomedica. 2019 May 1;39(s1):135-149.
• [15] In vitro evaluation of biomarkers of nephrotoxicity through gene expression using gentamicin. J Biochem Mol Toxicol. 2018 Sep;32(9):e22189. doi: 10.1002/jbt.22189. Epub 2018 Jul 10.
• [16] Stop codon read-through of a methylmalonic aciduria mutation. Mol Genet Metab. 2009 Aug;97(4):244-9. doi: 10.1016/j.ymgme.2009.04.004. Epub 2009 Apr 12.
• [17] Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int. 2003 Sep;64(3):923-32. doi: 10.1046/j.1523-1755.2003.00153.x.
• [18] Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15676-81. doi: 10.1073/pnas.0405155101. Epub 2004 Oct 21.
• [19] Deficiency of polycystin-2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells. FASEB J. 2004 May;18(7):884-6. doi: 10.1096/fj.03-0687fje. Epub 2004 Mar 4.
• [20] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [21] Organic Cation Transporter 2 Overexpression May Confer an Increased Risk of Gentamicin-Induced Nephrotoxicity. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5573-80. doi: 10.1128/AAC.00907-16. Print 2016 Sep.