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

General Information of Drug (ID: DMTBKF3)

• Drug Name: Piperacillin Drug Info
• Synonyms: PIPC; Peperacillin; Peracin; Pipercillin; Pipracil; Pipril; PIPERACILLIN SODIUM; Piperacillin Monosodium Salt; Piperacillin anhydrous; Cl-227193; Peracin (TN); Piperacillin (INN); Piperacillin (anhydrous); Pipracil, Piper; T-1220; Zobactin (TN); (2S,5R,6R)-6-[[(2R)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[(2R)-2-{[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino}-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S-(2alpha,5alpha,6beta(S*)))-6-(((((4-Ethyl-2,3-dioxopiperazin-1-yl)carbonyl)amino)phenylacetyl)amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid; 4-ethyl-2,3-dioxopiperazine carbonyl ampicillin; 6-(D-(-)-alpha-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)phenylacetamido)penicillanicacid; 6beta-{(2R)-2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carboxamido]-2-phenylacetamido}-2,2-dimethylpenam-3alpha-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis		Approved	[1]
Appendicitis	DB10	Approved	[1]
Bacteremia	1A73	Approved	[1]
Bacterial infection	1A00-1C4Z	Approved	[2]
Peritonitis		Approved	[1]
Pseudomonas aeruginosa infectious disease		Approved	[1]
Staphylococcus aureus infection		Approved	[1]
Urinary tract infection	GC08	Approved	[1]
Pelvic inflammatory disease	GA05	Investigative	[1]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 43672
  ChEBI ID: CHEBI:8232
  CAS Number: CAS 61477-96-1
  TTD Drug ID: DMTBKF3
  VARIDT Drug ID: DR00857
  INTEDE Drug ID: DR2410

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	[8]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[9]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[10]
Ticarcillin	DM4ME02	Aspiration pneumonia		Approved	[11]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[12]
Meropenem	DM62UHC	Bacterial infection	1A00-1C4Z	Approved	[10]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[13]
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[15]
Carbenicillin	DMLEDNK	Infection of the upper and lower urinary tract	GC08	Approved	[16]

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	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[18]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[19]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[20]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[21]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[4]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[22]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[18]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[20]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[20]

Drug(s) Metabolized By Beta-lactamase (blaB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[23]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[5]
Cefalotin	DMVYSLE	Bacteremia	1A73	Approved	[5]
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[5]
Cephaloridine	DM4Y95F	Gram-positive bacterial infection	1B74-1G40	Withdrawn from market	[5]
Tazobactam	DM3XNUI	Appendicitis	DB10	Approved	[7]
Imipenem	DMI9FBP	Bacteremia	1A73	Approved	[24]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[6]
Tazobactam	DM3XNUI	Appendicitis	DB10	Approved	[6]
Cefotaxime	DMEB837	Bacteremia	1A73	Approved	[6]

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 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Beta-lactamase (blaB)	DET9I1W	BLAC_BACUN	Substrate	[5]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Substrate	[6]
Beta-lactamase (blaB)	DEEZ5CV	BLO1_KLEOX	Substrate	[7]

References

• [1] Piperacillin FDA Label
• [2] Zosyn (piperacillin/tazobactam) reformulation: Expanded compatibility and coadministration with lactated Ringer's solutions and selected aminoglycosides. Ther Clin Risk Manag. 2008 Apr;4(2):303-14.
• [3] In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enter... J Infect Dis. 2004 Dec 15;190(12):2162-6.
• [4] 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.
• [5] Purification and characterization of a new beta-lactamase from Bacteroides uniformis. Antimicrob Agents Chemother. 1995 Jul;39(7):1458-61.
• [6] Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens. Niger J Clin Pract. 2019 Jan;22(1):125-130.
• [7] Characterization of piperacillin/tazobactam-resistant klebsiella oxytoca recovered from a nosocomial outbreak. PLoS One. 2015 Nov 5;10(11):e0142366.
• [8] Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob Agents Chemother. 2002 May;46(5):1273-80.
• [9] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus. Jpn J Antibiot. 1993 Jun;46(6):421-7.
• [12] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [13] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [14] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [15] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [16] 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.
• [17] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [18] 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.
• [19] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [20] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [21] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [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] 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.
• [24] Antibiotic therapy for inducible AmpC beta-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides? Int J Antimicrob Agents. 2012 Oct;40(4):297-305.