Details of the Drug Combination

General Information of Drug Combination (ID: DCLDLH4)

• Drug Combination Name: Framycetin + Cefazolin
• Indication: Colostomy; Status: Phase 1 [1]
• Component Drugs:
  Framycetin (DMF8DNE): Small molecular drug
  Cefazolin (DMPDYFR): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Framycetin

Disease Entry	ICD 11	Status	REF
Acute liver failure	DB91	Approved	[2]
Alcoholic cirrhosis of liver	DB94	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Blepharoconjunctivitis	N.A.	Approved	[4]
Corneal abrasion	NA06.4	Approved	[4]
Hepatic coma	N.A.	Approved	[4]
Hepatic encephalopathy	DB99.5	Approved	[4]
Keratitis	N.A.	Approved	[5]
Urinary tract infection	GC08	Approved	[6]
Uveitis	9A96.Z	Investigative	[4]

Framycetin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 16S ribosomal RNA (Bact 16S rRNA)	TT38DW5	NOUNIPROTAC	Binder	[9]
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[10]

Framycetin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Metabolism	[11]
Aminoglycoside N-acetyltransferase (aacC2)	DEJADS9	AAC6_ACIBA	Metabolism	[11]

Framycetin Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Increases Expression	[12]
N-alpha-acetyltransferase 15, NatA auxiliary subunit (NAA15)	OT53SIZG	NAA15_HUMAN	Increases ADR	[13]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases ADR	[13]

Indication(s) of Cefazolin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[7]
Bacterial infection	1A00-1C4Z	Approved	[8]
Cholangitis	N.A.	Approved	[7]
Staphylococcal pneumonia	N.A.	Approved	[7]

Cefazolin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[14]

Cefazolin Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[15]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[16]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[17]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[18]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[18]

Cefazolin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[19]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Metabolism	[20]
Beta-lactamase (blaB)	DE7IH52	AMPC_CITFR	Metabolism	[21]
Beta-lactamase (blaB)	DENJ2SQ	BLAB_BACFG	Metabolism	[22]

References

• [1] ClinicalTrials.gov (NCT03593252) Bowel Preparation in Elective Pediatric Colorectal Surgery
• [2] 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: 709).
• [3] Drug information of Framycetin, 2008. eduDrugs.
• [4] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [5] Bacterial isolates, antimicrobial susceptibility, and clinical characteristics of bacterial keratitis in dogs presenting to referral practice in Australia. Vet Ophthalmol. 2016 Sep;19(5):418-26.
• [6] Prostatectomy and infection. J Urol. 1971 Dec;106(6):910-2.
• [7] Cefazolin FDA Label
• [8] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065244.
• [9] Antistaphylococcal activity of gentamicin. Minerva Med. 1975 Dec 8;66(84):4505-26.
• [10] Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin. Arch Microbiol. 2008 May;189(5):441-9.
• [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] 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.
• [13] 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.
• [14] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [15] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [16] Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
• [17] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [18] Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
• [19] Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia. Drug Metab Dispos. 2002 Oct;30(10):1123-8.
• [20] Analysis of the drug-resistant characteristics of Klebsiella pneumoniae isolated from the respiratory tract and CTX-M ESBL genes. Genet Mol Res. 2015 Oct 5;14(4):12043-8.
• [21] Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes. J Microbiol Immunol Infect. 2018 Aug;51(4):565-572.
• [22] Prevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolates. Clin Microbiol Infect. 2019 Sep;25(9):1156.e9-1156.e13.