Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM42W1B)

• Drug Name: Cefmetazole Drug Info
• Synonyms: CMZ; Cefmetazolo; Cefmetazolum; Cefmetazole Monosodium Salt; CS 1170; SKF 83088; U 72791; CS-1170; Cefmetazole [USAN:INN]; Cefmetazolo [INN-Spanish]; Cefmetazolum [INN-Latin]; U-72791A; Cefmetazole (USP/INN); (6R,7S)-7-(2-((Cyanomethyl)thio)acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; (6R,7S)-7-(2-((Cyanomethyl)thio)acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thiomethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, sodium salt; (6R,7S)-7-({[(cyanomethyl)sulfanyl]acetyl}amino)-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7S)-7-({[(cyanomethyl)thio]acetyl}amino)-7-(methyloxy)-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7S)-7-[[2-(cyanomethylsulfanyl)acetyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 6beta-{[(cyanomethyl)sulfanyl]acetamido}-6alpha-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}ceph-3-em-4-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
Pneumonia	CA40	Approved	[2]
Staphylococcal pneumonia		Approved	[2]
Urinary tract infection	GC08	Approved	[2]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 42008
  ChEBI ID: CHEBI:3489
  CAS Number: CAS 56796-20-4
  TTD Drug ID: DM42W1B
  VARIDT Drug ID: DR00539

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial Penicillin binding protein 3 (Bact mrcA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aztreonam	DMDNJHG	Bacterial infection	1A00-1C4Z	Approved	[6]
Cefotiam	DMF5HU6	Respiratory tract infection	CA45	Approved	[7]
Latamoxef	DMANL0D	Bacterial infection	1A00-1C4Z	Approved	[3]
Mezlocillin	DMY5JEP	Acute gonococcal cervicitis		Approved	[8]
Moxalactam Disodium	DMYKUNR	Bacterial infection	1A00-1C4Z	Approved	[9]
Cefmenoxime	DMPLY7B	Bacterial infection	1A00-1C4Z	Approved	[10]
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[11]
LYS228	DM23Y6K	Urinary tract infection	GC08	Phase 2	[12]
Cephalosporin C	DMYW3ZG	Discovery agent	N.A.	Investigative	[13]
PCNOTAXIME GROUP	DMGS6YH	Discovery agent	N.A.	Investigative	[14]

Drug(s) Transported By Peptide transporter 1 (SLC15A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[16]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[17]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[18]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[19]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[20]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[4]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[16]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[18]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[18]

Drug(s) Transported By Organic anion transporting polypeptide 1B3 (SLCO1B3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[21]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[25]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[26]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[27]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[28]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein 3 (Bact mrcA)	TT85JMW	FTSI_ECOLI	Binder	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[4]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[5]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050637.
• [2] Cefmetazole FDA Label
• [3] Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9.
• [4] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [5] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes. Biol Pharm Bull. 2011;34(3):389-95.
• [6] Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol. 2003 Jan;47(2):539-47.
• [7] Genetic analyses of beta-lactamase negative ampicillin-resistant strains of Haemophilus influenzae isolated in Okinawa, Japan. Jpn J Infect Dis. 2006 Feb;59(1):36-41.
• [8] Bactericidal effect of piperacillin alone and combined. Presse Med. 1986 Dec 20;15(46):2297-302.
• [9] Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12.
• [10] In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity. Antimicrob Agents Chemother. 1988 May;32(5):693-701.
• [11] Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 2001 Jun;45(6):1693-9.
• [12] Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18.
• [13] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [14] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [15] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [16] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [17] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [18] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [19] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [20] 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.
• [21] LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
• [22] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [23] Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
• [24] Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53.
• [25] Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
• [26] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [27] FDA Drug Development and Drug Interactions
• [28] Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.