Identification

Name
Meticillin
Accession Number
DB01603
Type
Small Molecule
Groups
Approved, Investigational
Description

One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection. [PubChem]

Structure
Thumb
Synonyms
  • (2,6-Dimethoxyphenyl)penicillin
  • (2S,5R,6R)-6-[(2,6-Dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • 6-(2,6-Dimethoxybenzamido)penicillanic acid
  • 6beta-(2,6-Dimethoxybenzamido)penicillanic acid
  • Methicillin
  • Methicillinum
  • Methycillin
  • Meticilina
  • Meticillin
  • Meticilline
  • Meticillinum
Product Ingredients
IngredientUNIICASInChI Key
Methicillin sodiumAO9YF4MN307246-14-2NRZPASQBOYNGHR-HWROMZCQSA-M
International/Other Brands
Dimocillin / Metacillin
Categories
UNII
Q91FH1328A
CAS number
61-32-5
Weight
Average: 380.415
Monoisotopic: 380.104207072
Chemical Formula
C17H20N2O6S
InChI Key
RJQXTJLFIWVMTO-TYNCELHUSA-N
InChI
InChI=1S/C17H20N2O6S/c1-17(2)12(16(22)23)19-14(21)11(15(19)26-17)18-13(20)10-8(24-3)6-5-7-9(10)25-4/h5-7,11-12,15H,1-4H3,(H,18,20)(H,22,23)/t11-,12+,15-/m1/s1
IUPAC Name
(2S,5R,6R)-6-(2,6-dimethoxybenzamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(OC)C=CC=C1OC)C(O)=O

Pharmacology

Indication

Used to treat infections caused by susceptible Gram-positive bacteria, particularly beta-lactamase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins.

Pharmacodynamics

Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is no longer clinically used. Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe Staphylococcus aureus strains resistant to all penicillins.

Mechanism of action

Like other beta-lactam antibiotics, meticillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.

TargetActionsOrganism
AMecA PBP2' (penicillin binding protein 2')
inhibitor
Staphylococcus aureus
APenicillin-binding protein 2a
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 1b
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 2B
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 3
inhibitor
Streptococcus pneumoniae
APenicillin-binding protein 1A
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Absorption

Not absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic (20-40%).

Route of elimination
Not Available
Half life

25-60 minutes

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
  • Gram-positive Bacteria
  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Staphylococcus aureus
  • Staphylococcus epidermidis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinMeticillin may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinMeticillin may increase the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarinMeticillin may increase the anticoagulant activities of 4-hydroxycoumarin.
AcemetacinAcemetacin may decrease the excretion rate of Meticillin which could result in a higher serum level.
AcenocoumarolMeticillin may increase the anticoagulant activities of Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Meticillin.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Meticillin.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Meticillin.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Meticillin.
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Meticillin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015541
KEGG Compound
C07177
PubChem Compound
6087
PubChem Substance
46508973
ChemSpider
5862
BindingDB
50103523
ChEBI
6827
ChEMBL
CHEMBL575
Therapeutic Targets Database
DAP001170
PharmGKB
PA164777034
HET
MII
Wikipedia
Methicillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CF03 — Meticillin
PDB Entries
3kp4

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.22HANSCH,C ET AL. (1995)
pKa2.77SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.31 mg/mLALOGPS
logP1.79ALOGPS
logP0.79ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)2.96ChemAxon
pKa (Strongest Basic)-1.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area105.17 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.4 m3·mol-1ChemAxon
Polarizability37.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9304
Blood Brain Barrier-0.9958
Caco-2 permeable-0.6628
P-glycoprotein substrateSubstrate0.5813
P-glycoprotein inhibitor INon-inhibitor0.9099
P-glycoprotein inhibitor IINon-inhibitor0.9535
Renal organic cation transporterNon-inhibitor0.9476
CYP450 2C9 substrateNon-substrate0.7962
CYP450 2D6 substrateNon-substrate0.8715
CYP450 3A4 substrateNon-substrate0.5144
CYP450 1A2 substrateNon-inhibitor0.8626
CYP450 2C9 inhibitorNon-inhibitor0.8793
CYP450 2D6 inhibitorNon-inhibitor0.921
CYP450 2C19 inhibitorNon-inhibitor0.8738
CYP450 3A4 inhibitorNon-inhibitor0.7747
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.95
Ames testNon AMES toxic0.8607
CarcinogenicityNon-carcinogens0.6826
BiodegradationNot ready biodegradable0.9376
Rat acute toxicity1.8893 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9995
hERG inhibition (predictor II)Non-inhibitor0.8358
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 dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Penicillins / N-acyl-alpha amino acids and derivatives / Dimethoxybenzenes / Benzamides / Anisoles / Benzoyl derivatives / Phenoxy compounds / Alkyl aryl ethers / Tertiary carboxylic acid amides / Thiazolidines
show 12 more
Substituents
Alpha-dipeptide / Penicillin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Dimethoxybenzene / M-dimethoxybenzene / Benzoic acid or derivatives / Benzamide / Penam / Phenoxy compound
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:6827)

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
mecA
Uniprot ID
Q53707
Uniprot Name
MecA PBP2' (penicillin binding protein 2')
Molecular Weight
76265.485 Da
References
  1. Gardete S, de Lencastre H, Tomasz A: A link in transcription between the native pbpB and the acquired mecA gene in a strain of Staphylococcus aureus. Microbiology. 2006 Sep;152(Pt 9):2549-58. [PubMed:16946250]
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring acyl groups
Specific Function
Not Available
Gene Name
pbp2a
Uniprot ID
Q8DNB6
Uniprot Name
Penicillin-binding protein 2a
Molecular Weight
80797.94 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring acyl groups
Specific Function
Not Available
Gene Name
pbp1b
Uniprot ID
Q7CRA4
Uniprot Name
Penicillin-binding protein 1b
Molecular Weight
89479.92 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Not Available
Specific Function
Penicillin binding
Gene Name
penA
Uniprot ID
P0A3M6
Uniprot Name
Penicillin-binding protein 2B
Molecular Weight
73872.305 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Streptococcus pneumoniae
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not Available
Gene Name
pbp3
Uniprot ID
Q75Y35
Uniprot Name
Penicillin-binding protein 3
Molecular Weight
45209.84 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Cell wall formation.
Gene Name
pbpA
Uniprot ID
Q8DR59
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
79700.9 Da
References
  1. Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]

Drug created on August 29, 2007 12:47 / Updated on October 01, 2018 16:39