Ceftobiprole
Identification
- Summary
Ceftobiprole is a cephalosporin antibiotic used to treat both community and hospital-acquired pneumonia caused by susceptible bacteria.
- Generic Name
- Ceftobiprole
- DrugBank Accession Number
- DB04918
- Background
Ceftobiprole is a cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus. It was discovered by Basilea Pharmaceutica and is being developed by Johnson & Johnson Pharmaceutical Research and Development. Ceftobiprole is the first cephalosporin to demonstrate clinical efficacy in patients with infections due to methicillin-resistant staphylococci and, if approved by regulatory authorities, is expected to be a useful addition to the armamentarium of agents for the treatment of complicated skin infections and pneumonia.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 534.57
Monoisotopic: 534.110372808 - Chemical Formula
- C20H22N8O6S2
- Synonyms
- Ceftobiprol
- Ceftobiprole
- External IDs
- BAL-9141
- BAL-9141-000
- BAL-9141000
- BAL9141-000
- RO 63-9141
- RO-63-9141
- RO-639141
Pharmacology
- Indication
For the treatment of serious bacterial infections in hospitalised patients.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Community acquired pneumonia •••••••••••• ••••• Treatment of Hospital acquired pneumonia •••••••••••• ••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant Staphylococcus aureus.
- Mechanism of action
Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan.
Target Actions Organism UMecA Not Available Staphylococcus aureus UPenicillin-binding protein 2x Not Available Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) UPeptidoglycan synthase FtsI Not Available Escherichia coli (strain K12) - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Ceftobiprole may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole. Aceclofenac The risk or severity of nephrotoxicity can be increased when Ceftobiprole is combined with Aceclofenac. Acemetacin The risk or severity of nephrotoxicity can be increased when Ceftobiprole is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Ceftobiprole is combined with Acenocoumarol. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Lactams
- Sub Class
- Beta lactams
- Direct Parent
- Cephalosporins
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / 1,3-thiazines / Pyrrolidine-2-ones / N-alkylpyrrolidines / Thiadiazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Ketoximes / Secondary carboxylic acid amides / Amino acids show 12 more
- Substituents
- 2-pyrrolidone / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azetidine / Azole / Carbonyl group show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Enteric bacteria and other eubacteria
Chemical Identifiers
- UNII
- 5T97333YZK
- CAS number
- 209467-52-7
- InChI Key
- VOAZJEPQLGBXGO-SDAWRPRTSA-N
- InChI
- InChI=1S/C20H22N8O6S2/c21-20-24-14(26-36-20)11(25-34)15(29)23-12-17(31)28-13(19(32)33)9(7-35-18(12)28)5-8-2-4-27(16(8)30)10-1-3-22-6-10/h5,10,12,18,22,34H,1-4,6-7H2,(H,23,29)(H,32,33)(H2,21,24,26)/b8-5+,25-11-/t10-,12-,18-/m1/s1
- IUPAC Name
- (6R,7R)-7-[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(N-hydroxyimino)acetamido]-8-oxo-3-{[(3E,3'R)-2-oxo-[1,3'-bipyrrolidin]-3-ylidene]methyl}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
- SMILES
- [H][C@@]1(NC(=O)C(=N/O)\C2=NSC(N)=N2)C(=O)N2C(C(O)=O)=C(CS[C@]12[H])\C=C1/CCN(C1=O)[C@]1([H])CCNC1
References
- General References
- Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K: Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007 Jul;51(7):2621-4. Epub 2007 Apr 30. [Article]
- Noel GJ: Clinical profile of ceftobiprole, a novel beta-lactam antibiotic. Clin Microbiol Infect. 2007 Jun;13 Suppl 2:25-9. [Article]
- Yun HC, Ellis MW, Jorgensen JH: Activity of ceftobiprole against community-associated methicillin-resistant Staphylococcus aureus isolates recently recovered from US military trainees. Diagn Microbiol Infect Dis. 2007 Dec;59(4):463-6. Epub 2007 Oct 29. [Article]
- Lin G, Appelbaum PC: Activity of ceftobiprole compared with those of other agents against Staphylococcus aureus strains with different resistotypes by time-kill analysis. Diagn Microbiol Infect Dis. 2008 Feb;60(2):233-5. Epub 2007 Nov 7. [Article]
- Noel GJ, Strauss RS, Amsler K, Heep M, Pypstra R, Solomkin JS: Results of a double-blind, randomized trial of ceftobiprole treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Antimicrob Agents Chemother. 2008 Jan;52(1):37-44. Epub 2007 Oct 22. [Article]
- External Links
- KEGG Drug
- D08885
- PubChem Compound
- 12993649
- PubChem Substance
- 175426903
- ChemSpider
- 23350302
- ChEBI
- 140407
- ChEMBL
- CHEMBL520642
- ZINC
- ZINC000004424091
- Wikipedia
- Ceftobiprole
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Acute Bacterial Skin and Skin Structure Infection (ABSSSI) 1 3 Completed Treatment Community Acquired Pneumonia (CAP) / Nosocomial Pneumonia 1 3 Recruiting Treatment Sepsis, Neonatal 1 1 Completed Basic Science Antimicrobial Therapy / Cephalosporins / Drug Resistance 1 1 Completed Basic Science Obesity / Staphylococcal Skin Infections / Streptococcal Infections 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Intravenous 666.60 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.159 mg/mL ALOGPS logP -1.3 ALOGPS logP -4.7 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 2.89 Chemaxon pKa (Strongest Basic) 10.4 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 11 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 203.44 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 131.04 m3·mol-1 Chemaxon Polarizability 51.22 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9848 Blood Brain Barrier - 0.9231 Caco-2 permeable - 0.6329 P-glycoprotein substrate Substrate 0.821 P-glycoprotein inhibitor I Non-inhibitor 0.8638 P-glycoprotein inhibitor II Non-inhibitor 0.9971 Renal organic cation transporter Non-inhibitor 0.9155 CYP450 2C9 substrate Non-substrate 0.8546 CYP450 2D6 substrate Non-substrate 0.7979 CYP450 3A4 substrate Non-substrate 0.5567 CYP450 1A2 substrate Non-inhibitor 0.686 CYP450 2C9 inhibitor Non-inhibitor 0.7322 CYP450 2D6 inhibitor Non-inhibitor 0.8646 CYP450 2C19 inhibitor Non-inhibitor 0.6778 CYP450 3A4 inhibitor Non-inhibitor 0.8981 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9212 Ames test Non AMES toxic 0.5598 Carcinogenicity Non-carcinogens 0.8598 Biodegradation Ready biodegradable 0.7278 Rat acute toxicity 2.4586 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7721 hERG inhibition (predictor II) Non-inhibitor 0.7278
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 244.0475815 predictedDarkChem Lite v0.1.0 [M-H]- 219.90514 predictedDeepCCS 1.0 (2019) [M+H]+ 245.3068815 predictedDarkChem Lite v0.1.0 [M+H]+ 222.11086 predictedDeepCCS 1.0 (2019) [M+Na]+ 245.1662815 predictedDarkChem Lite v0.1.0 [M+Na]+ 228.02339 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Staphylococcus aureus
- Pharmacological action
- Unknown
- General Function
- Transferase activity, transferring glycosyl groups
- Specific Function
- Not Available
- Gene Name
- mecA
- Uniprot ID
- Q7DHH4
- Uniprot Name
- MecA
- Molecular Weight
- 76102.075 Da
References
- Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K: Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007 Jul;51(7):2621-4. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
- Pharmacological action
- Unknown
- General Function
- Penicillin binding
- Specific Function
- Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins.
- Gene Name
- pbpX
- Uniprot ID
- P14677
- Uniprot Name
- Penicillin-binding protein 2x
- Molecular Weight
- 82312.475 Da
References
- Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K: Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007 Jul;51(7):2621-4. Epub 2007 Apr 30. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Unknown
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan fr...
- Gene Name
- ftsI
- Uniprot ID
- P0AD68
- Uniprot Name
- Peptidoglycan synthase FtsI
- Molecular Weight
- 63876.925 Da
References
- Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K: Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007 Jul;51(7):2621-4. Epub 2007 Apr 30. [Article]
Drug created at October 21, 2007 22:23 / Updated at March 18, 2024 16:48