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

General Information of Drug (ID: DMHSJB4)

• Drug Name: Cyclacillin Drug Info
• Synonyms: Aminocyclohexylpenicillin; Bastcillin; Calthor; Ciclacilina; Ciclacillin; Ciclacilline; Ciclacillinum; Ciclacillum; Citosarin; Cyclapen; Noblicil; Orfilina; Peamezin; Syngacillin; Ultracillin; Vastcillin; Vipicil; Wyvital; Aminocyclohexyl penicillin; Cyclacillin [USAN]; AC 98; WY 4508; WY4508; C-12104; Ciclacilina [INN-Spanish]; Ciclacilline [INN-French]; Ciclacillinum [INN-Latin]; Cyclacillin (USAN); Cyclapen (TN); Cyclapen-W; Vastcillin (TN); Wy-4508; Ciclacillin (JP15/INN); Cyclapen-W (TN); (1-Aminocyclohexyl)penicillin; (2S,5R,6R)-6-[(1-aminocyclohexanecarbonyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[(1-aminocyclohexyl)carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-(1-aminocyclohexanecarboxamido)-3,3-dimethyl-7-oxo-(8CI); 6-(1-Aminocyclohexanecarboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid; 6-(1-Aminocyclohexanecarboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(1-Aminocyclohexanecarboxamido)penicillanic acid; 6-(1-Aminocyclohexylcarboxamido)penicillanic acid; 6beta-(1-aminocyclohexanecarboxamido)-2,2-dimethylpenam-3alpha-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
Bronchitis	CA20	Approved	[2]
Urinary tract infection	GC08	Approved	[2]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 19003
  ChEBI ID: CHEBI:31444
  CAS Number: CAS 3485-14-1
  TTD Drug ID: DMHSJB4
  VARIDT Drug ID: DR00480

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	[5]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[6]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[7]
Ticarcillin	DM4ME02	Aspiration pneumonia		Approved	[8]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[9]
Meropenem	DM62UHC	Bacterial infection	1A00-1C4Z	Approved	[7]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[10]
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[12]
Carbenicillin	DMLEDNK	Infection of the upper and lower urinary tract	GC08	Approved	[13]

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	[14]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[15]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[16]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[17]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[18]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[19]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[20]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[15]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[17]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[17]

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	[14]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[4]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[21]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[22]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[23]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[4]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[24]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[14]
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[25]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[26]

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	[4]

References

• [1] 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: 4817).
• [2] Cyclacillin FDA Label
• [3] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [4] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [5] 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.
• [6] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] 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.
• [9] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [10] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [11] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [12] 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.
• [13] 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.
• [14] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [15] 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.
• [16] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [17] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [18] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [23] 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.
• [24] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [25] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [26] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.