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

General Information of Drug (ID: DMWV2AG)

• Drug Name: Ceftibuten Drug Info
• Synonyms: CETB; Cedax; Ceftem; Ceftibutene; Ceftibuteno; Ceftibutenum; Cephem; Ceprifran; Isocef; Keimax; Antibiotic 7432S; S 7432; Sch 39720; Cedax (TN); Ceftibutene [INN-French]; Ceftibuteno [INN-Spanish]; Ceftibutenum [INN-Latin]; Cephalosporin 7432-S; Cis-Ceftibutin; Cis-ceftibuten; Sch-39720; Trans-Ceftibuten; Ceftibuten(USAN/INN); Ceftibuten [USAN:INN:BAN]; (+)-(6R,7R)-7-((Z)-2-(2-Amino-4-thiazolyl)-4-carboxycrotonamido)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(E)-2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(Z)-2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-4-carboxybut-2-enoyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7-[[(E)-2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7-[[(Z)-2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7-[[2-(2-amino-1,3-thiazol-4-yl)-5-hydroxy-5-oxopent-2-enoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7432-S; 7beta-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-4-carboxybut-2-enoyl]amino}-3,4-didehydrocepham-4-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[1]
Chronic bronchitis	CA20.1	Approved	[2]
Pars planitis		Approved	[1]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 5282242
  ChEBI ID: CHEBI:3510
  CAS Number: CAS 97519-39-6
  TTD Drug ID: DMWV2AG
  VARIDT Drug ID: DR00537
  ACDINA Drug ID: D00111

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial Penicillin binding protein (Bact PBP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[7]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[8]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[9]
Ticarcillin	DM4ME02	Aspiration pneumonia		Approved	[10]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[11]
Meropenem	DM62UHC	Bacterial infection	1A00-1C4Z	Approved	[9]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[12]
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[14]
Carbenicillin	DMLEDNK	Infection of the upper and lower urinary tract	GC08	Approved	[15]

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	[16]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[17]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[18]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[19]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[20]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[21]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[22]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[17]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[19]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[19]

Drug(s) Transported By Peptide transporter 2 (SLC15A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[16]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[4]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[23]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[24]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[25]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[4]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[26]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[16]
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[27]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[28]

Drug(s) Affected By Organic anion transporter 3 (SLC22A8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Valsartan	DMREUQ6	Chronic heart failure	BD1Z	Approved	[29]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[30]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[31]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[32]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[33]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[33]
Cefdinir	DMJ7A0H	Bacterial infection	1A00-1C4Z	Approved	[6]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[6]
Famotidine	DMRL3AB	Gastric ulcer	DA60	Approved	[34]
Tetracycline	DMZA017	Acne vulgaris	ED80	Approved	[35]

Drug(s) Affected By Solute carrier family 22 member 6 (SLC22A6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[30]
Salicyclic acid	DM2F8XZ	Acne vulgaris	ED80	Approved	[36]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[36]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[37]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[36]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[36]
Succinic acid	DMDWICP	Malnutrition	5B50-5B71	Approved	[38]
Mefenamic acid	DMK7HFI	Dysmenorrhea	GA34.3	Approved	[36]
Probenecid	DMMFWOJ	Acute gonococcal cervicitis		Approved	[39]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[4]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Regulation of Drug Effects	[6]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Regulation of Drug Effects	[6]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [5] Increased protein level of PEPT1 intestinal H+-peptide cotransporter upregulates absorption of glycylsarcosine and ceftibuten in 5/6 nephrectomized rats. Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G664-70.
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• [15] Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23.
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• [18] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [19] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
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• [21] 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.
• [22] 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.
• [23] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [24] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [25] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [26] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [27] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
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• [29] Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress. Toxicology. 2023 Jan 1;483:153387. doi: 10.1016/j.tox.2022.153387. Epub 2022 Dec 1.
• [30] P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate. Toxicol Appl Pharmacol. 2016 Sep 1;306:27-35. doi: 10.1016/j.taap.2016.06.030. Epub 2016 Jul 1.
• [31] Intracellular concentrations determine the cytotoxicity of adefovir, cidofovir and tenofovir. Toxicol In Vitro. 2015 Feb;29(1):251-8. doi: 10.1016/j.tiv.2014.10.019.
• [32] Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
• [33] A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
• [34] Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30.
• [35] Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.
• [36] Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2002 Nov;303(2):534-9.
• [37] Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020 Jun 1;175(2):279-291. doi: 10.1093/toxsci/kfaa033.
• [38] Lack of efflux of diglycolic acid from proximal tubule cells leads to its accumulation and to toxicity of diethylene glycol. Toxicol Lett. 2023 Apr 15;379:48-55. doi: 10.1016/j.toxlet.2023.03.007. Epub 2023 Mar 22.
• [39] Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.