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

General Information of Drug (ID: DMVGPMX)

• Drug Name: Fosfomycin Drug Info
• Synonyms: FCM; Phosphomycin; Phosphonemycin; Phosphonomycin; Priomicina; Veramina; Disodium fosfomycin; Disodium phosphonomycin; Fosfocina disodium salt; Fosfomycin disodium; Fosfomycin disodium salt; Fosfomycin sodium; Fosfomycin sodium salt; Fosmicin S; Phosphomycin disodium salt; Phosphonomycin disodium salt; Phosphonomycin sodium; Sodium fosfomycin; MK 955; FOM-Na; Fosfomycin sodium (JP15); Fosmicin S (TN); Fosfomycin (USAN/INN); L-cis-1,2-epoxypropylphosphonic acid; Disodium (1R,2S)-(1,2-epoxypropyl)phosphonate; Disodium[(2r,3s)-3-methyloxiran-2-yl]phosphonate; [(2R,3S)-3-methyloxiran-2-yl]phosphonic acid; Phosphonic acid, (3-methyloxiranyl)-, disodium salt, (2R-cis)-(9CI); (-)-(1R,2S)-(1,2-Epoxypropyl)phosphonicacid; (1R,2S)(-)-(1,2-Epoxypropyl)phosphonic acid disodium salt; (1R,2S)-(1,2-Epoxypropyl)phosphonic acid; (1R,2S)-epoxypropylphosphonate; (1R,2S)-epoxypropylphosphonic acid; (2R-cis)-(3-Methyloxiranyl)phosphonic acid disodium salt

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 446987
  ChEBI ID: CHEBI:28915
  CAS Number: CAS 23155-02-4
  TTD Drug ID: DMVGPMX
  INTEDE Drug ID: DR0749

Molecule-Related Drug Atlas

Drug(s) Metabolized By Glutathione S-transferase alpha-1 (GSTA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[8]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[9]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[10]
Clofibrate	DMPC1J7	Dysbetalipoproteinemia	5C80.2	Approved	[11]
Trabectedin	DMG3Y89	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Busulfan	DMXYJ9C	Myeloproliferative syndrome	2A22	Approved	[13]
Artemisinin	DMOY7W3	Malaria	1F40-1F45	Approved	[14]
Ethacrynic acid	DM60QMR	High blood pressure	BA00	Approved	[15]
Tacrine	DM51FY6	Alzheimer disease	8A20	Approved	[16]

Drug(s) Targeting Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Uridine-Diphosphate-N-Acetylglucosamine	DMEQSTP	Discovery agent	N.A.	Investigative	[17]
RWJ-3981	DMBVLCQ	Gram-positive bacterial infection	1B74-1G40	Investigative	[18]
RWJ-140998	DMP7SI9	Gram-positive bacterial infection	1B74-1G40	Investigative	[18]
Aminomethylcyclohexane	DMNX9FC	Discovery agent	N.A.	Investigative	[19]
EUPATORIOPICRIN	DM068CY	Discovery agent	N.A.	Investigative	[20]
CNICIN	DMEVM0J	Discovery agent	N.A.	Investigative	[20]
L-Iso-Aspartate	DM26AB4	Discovery agent	N.A.	Investigative	[19]
Cyclohexylammonium Ion	DMYQH2N	Discovery agent	N.A.	Investigative	[19]
CYNAROPICRIN	DMG0PHU	Discovery agent	N.A.	Investigative	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)	TTICX3S	MURA_ECOLI	Inhibitor	[2] , [3] , [4] , [5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Glutathione S-transferase alpha-1 (GSTA1) Main DME	DE4ZHS1	GSTA1_HUMAN	Substrate	[6]

References

• [1] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [2] Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63.
• [3] Conditional lethal amber mutations in essential Escherichia coli genes. J Bacteriol. 2004 May;186(9):2673-81.
• [4] In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28.
• [5] Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9.
• [6] Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria. Antimicrob Agents Chemother. 1988 Oct;32(10):1552-6.
• [7] Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin. Mol Cancer Ther. 2008 Oct;7(10):3247-55.
• [8] Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem. 2001 Aug 31;276(35):33061-5.
• [9] Retinoid X receptor alpha regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver. Mol Pharmacol. 2005 Dec;68(6):1590-6.
• [10] Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. Comp Biochem Physiol C. 1987;88(1):91-3.
• [11] Characterization and formation of the glutathione conjugate of clofibric acid. Drug Metab Dispos. 1995 Jan;23(1):119-23.
• [12] In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs. 2006 Jan;24(1):3-14.
• [13] Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004 Sep 1;104(5):1574-7.
• [14] Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
• [15] Purification and biochemical properties of glutathione S-transferase from Lactuca sativa. J Biochem Mol Biol. 2005 Mar 31;38(2):232-7.
• [16] Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther. 2000 Apr;67(4):432-7.
• [17] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [18] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [19] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [20] Sesquiterpene lactones are potent and irreversible inhibitors of the antibacterial target enzyme MurA. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5605-9.