Identification

Name
Latamoxef
Accession Number
DB04570
Type
Small Molecule
Groups
Approved, Investigational
Description

Broad- spectrum beta-lactam antibiotic similar in structure to the cephalosporins except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain cephalosporins. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections. [PubChem]

Structure
Thumb
Synonyms
  • Lamoxactam
  • Latamoxef
  • Latamoxefum
  • LMOX
  • moxalactam
  • Oxa-cephem
Product Ingredients
IngredientUNIICASInChI Key
Latamoxef disodium5APW73W3QZ64953-12-4GRIXGZQULWMCLU-HUTAOCTPSA-L
Categories
UNII
VUF6C936Z3
CAS number
64952-97-2
Weight
Average: 520.473
Monoisotopic: 520.101246958
Chemical Formula
C20H20N6O9S
InChI Key
JWCSIUVGFCSJCK-CAVRMKNVSA-N
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
IUPAC Name
(6R,7R)-7-[2-carboxy-2-(4-hydroxyphenyl)acetamido]-7-methoxy-3-{[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12OCC(CSC3=NN=NN3C)=C(N1C(=O)[C@]2(NC(=O)C(C(O)=O)C1=CC=C(O)C=C1)OC)C(O)=O

Pharmacology

Indication

Latamoxef is an oxacephem antibiotic usually grouped with the cephalosporins. It is used to treat bacterial infections. Latamoxef is primarily indicated in conditions like Bone and joint infection, GI infections, Gynecological infections, Meningitis, Respiratory tract infections, Septicaemia, Skin infections, Soft tissue infections, UTI.

Pharmacodynamics

Latamoxef works by inhibiting bacterial cell wall biosynthesis.

Mechanism of action

Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain (the penicillin-binding protein) by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that amoxicllin interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 3
inhibitor
Bacillus subtilis (strain 168)
UPenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
UPenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
UD-alanyl-D-alanine carboxypeptidase DacB
inhibitor
Escherichia coli (strain K12)
Absorption

Rapidly absorbed after oral administration.

Volume of distribution

8.51 L

Protein binding

40%

Metabolism
Not Available
Route of elimination

Renal Excretion accounts for 75 %

Half life

1.6 hours

Clearance
Not Available
Toxicity

Latamoxef produces potentially life-threatening effects which include Bleeding, Hypothrombinemia, Platelet dysfunctioning. which are responsible for the discontinuation of Latamoxef therapy. The symptomatic adverse reactions produced by Latamoxef are more or less tolerable and if they become severe, they can be treated symptomatically, these include Diarrhea, Skin rashes, Hematuria, Hyperuricemia, Pyuria, Raised serum creatinine.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Latamoxef is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Latamoxef is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Latamoxef is combined with 4-hydroxycoumarin.
AbacavirLatamoxef may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseLatamoxef may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacLatamoxef may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Latamoxef is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Latamoxef is combined with Acenocoumarol.
AcetaminophenLatamoxef may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Latamoxef.
Food Interactions
Not Available

References

General References
  1. Weitekamp MR, Aber RC: Prolonged bleeding times and bleeding diathesis associated with moxalactam administration. JAMA. 1983 Jan 7;249(1):69-71. [PubMed:6217353]
  2. Brown RB, Klar J, Lemeshow S, Teres D, Pastides H, Sands M: Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients. Arch Intern Med. 1986 Nov;146(11):2159-64. [PubMed:3778044]
External Links
Human Metabolome Database
HMDB0015574
KEGG Drug
D08109
KEGG Compound
C07231
PubChem Compound
47499
PubChem Substance
46505546
ChemSpider
43215
BindingDB
50370589
ChEBI
599928
ChEMBL
CHEMBL74632
Therapeutic Targets Database
DAP001181
PharmGKB
PA164743144
Wikipedia
Latamoxef
ATC Codes
J01DD06 — Latamoxef

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableNot Yet RecruitingNot AvailableCommunity Acquired Pneumonia (CAP)1
Not AvailableRecruitingNot AvailableChildren; Infection / Newborn; Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-0.58BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.751 mg/mLALOGPS
logP0.22ALOGPS
logP0.17ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)2.81ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area206.3 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity133.7 m3·mol-1ChemAxon
Polarizability47.27 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9253
Blood Brain Barrier-0.9914
Caco-2 permeable-0.7721
P-glycoprotein substrateSubstrate0.7268
P-glycoprotein inhibitor INon-inhibitor0.7989
P-glycoprotein inhibitor IIInhibitor0.5
Renal organic cation transporterNon-inhibitor0.8587
CYP450 2C9 substrateNon-substrate0.7914
CYP450 2D6 substrateNon-substrate0.8291
CYP450 3A4 substrateSubstrate0.5676
CYP450 1A2 substrateNon-inhibitor0.8075
CYP450 2C9 inhibitorNon-inhibitor0.7409
CYP450 2D6 inhibitorNon-inhibitor0.8614
CYP450 2C19 inhibitorNon-inhibitor0.7233
CYP450 3A4 inhibitorInhibitor0.5245
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.684
Ames testNon AMES toxic0.6673
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.9144
Rat acute toxicity2.2482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9759
hERG inhibition (predictor II)Non-inhibitor0.5569
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Phenylacetamides / Oxacephems / 1-hydroxy-2-unsubstituted benzenoids / Alkylarylthioethers / 1,3-dicarbonyl compounds / Dicarboxylic acids and derivatives / Tetrazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides
show 9 more
Substituents
N-acyl-alpha amino acid or derivatives / Phenylacetamide / Oxacephem / Aryl thioether / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Alkylarylthioether / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin, oxacephem (CHEBI:599928)

Targets

Kind
Protein
Organism
Bacillus subtilis (strain 168)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
pbpC
Uniprot ID
P42971
Uniprot Name
Penicillin-binding protein 3
Molecular Weight
74405.915 Da
References
  1. Ishikawa M, Miyauchi T, Yagi K, Chikaishi H, Fukuta Y, Miyake H, Harada M, Yogita S, Tashiro S: Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9. [PubMed:9841767]
  2. Labia R, Baron P, Masson JM: Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins. J Antimicrob Chemother. 1985 Jan;15(1):9-15. [PubMed:3918982]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
93635.545 Da
References
  1. Labia R, Baron P, Masson JM: Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins. J Antimicrob Chemother. 1985 Jan;15(1):9-15. [PubMed:3918982]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
94291.875 Da
References
  1. Labia R, Baron P, Masson JM: Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins. J Antimicrob Chemother. 1985 Jan;15(1):9-15. [PubMed:3918982]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction.
Gene Name
dacB
Uniprot ID
P24228
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacB
Molecular Weight
51797.85 Da
References
  1. Labia R, Baron P, Masson JM: Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins. J Antimicrob Chemother. 1985 Jan;15(1):9-15. [PubMed:3918982]

Drug created on September 06, 2007 17:50 / Updated on November 02, 2018 08:50