Details of the Drug

General Information of Drug (ID: DMANL0D)

• Drug Name: Latamoxef
• Synonyms: Festamoxin; LMOX; Lamoxactam; Latamoxefum; Moxalactam; Disodium Moxalactam; Lilly 127935; Ly127935; Sid 734787; Latamoxef (INN); Latamoxef [INN:BAN]; Latamoxefum [INN-Latin]; Oxa-cephem; S-6059; (6R,7R)-7-[[3-hydroxy-2-(4-hydroxyphenyl)-3-oxopropanoyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[carboxy(4-hydroxyphenyl)acetyl]amino}-7-(methyloxy)-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[carboxy(4-hydroxyphenyl)acetyl]amino}-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R-(6alpha,7alpha,7(S*)))-7-((Carboxy(4-hydroxyphenyl)acetyl)amino)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-oxa-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; 1-Oxacephalosporin; 7b-[2-carboxy-2-(4-hydroxyphenyl)acetamido]-7a-methoxy-3-[[(1-methyl-1h-tetrazol-5-yl)thio]methyl]-1-oxa-1-dethia-3-cephem-4-carboxylic acid; 7beta-(2-Carboxy-2-(4-hydroxyphenyl)acetamido)-7alpha-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-1-oxa-1-dethia-3-cephem-4-carboxylic acid

Indication

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

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 520.5
  Topological Polar Surface Area (xlogp); -0.6
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 13
• ADMET Property:
  Absorption: The drug is rapidly absorbed after oral administration [2]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: 85% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.72 mL/min/kg [5]
  Elimination: 76% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.6 hours [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 54.8942 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.39% [5]
  Vd: The volume of distribution (Vd) of drug is 8.51 L [7]
  Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [3]
• Chemical Identifiers:
  Formula: C20H20N6O9S
  IUPAC Name: (6R,7R)-7-[[2-carboxy-2-(4-hydroxyphenyl)acetyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  Canonical SMILES: CN1C(=NN=N1)SCC2=C(N3[C@@H]([C@@](C3=O)(NC(=O)C(C4=CC=C(C=C4)O)C(=O)O)OC)OC2)C(=O)O
  InChI: InChI=1S/C20H20N6O9S/c1-25-19(22-23-24-25)36-8-10-7-35-18-20(34-2,17(33)26(18)13(10)16(31)32)21-14(28)12(15(29)30)9-3-5-11(27)6-4-9/h3-6,12,18,27H,7-8H2,1-2H3,(H,21,28)(H,29,30)(H,31,32)/t12?,18-,20+/m1/s1
  InChIKey: JWCSIUVGFCSJCK-CAVRMKNVSA-N
• Cross-matching ID:
  PubChem CID: 47499
  ChEBI ID: CHEBI:599928
  CAS Number: 64952-97-2
  DrugBank ID: DB04570
  TTD ID: D0O5LU
  VARIDT ID: DR00654

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	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[8]

References

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• [2] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [3] BDDCS applied to over 900 drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [7] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [8] 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.
• [9] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [10] 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.
• [11] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [12] 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.
• [13] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [14] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [15] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [16] 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.
• [17] 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.
• [18] Bactericidal effect of piperacillin alone and combined. Presse Med. 1986 Dec 20;15(46):2297-302.
• [19] Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12.
• [20] In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity. Antimicrob Agents Chemother. 1988 May;32(5):693-701.
• [21] 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.
• [22] 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.
• [23] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [24] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.