Identification

Name
Cethromycin
Accession Number
DB06419
Type
Small Molecule
Groups
Investigational
Description

Cethromycin, trade name Restanza (initially known as ABT-773) is a ketolide antibiotic undergoing research for the treatment of community acquired pneumonia (CAP) and for the prevention of post-exposure inhalational anthrax, and was given an "orphan drug" status for this indication. Originally discovered and developed by Abbott, it was acquired by Advanced Life Sciences Inc. for further development. In June 2009,an FDA Anti-Infective Drugs Advisory Committee review found insufficient evidence for cethromycin efficacy in treatment of community acquired pneumonia, as the Phase 3 clinical trial followed standards that were updated after the clinical trial but three months prior to review. The committee did, however, find the drug safe to use.

Structure
Thumb
Synonyms
Not Available
External IDs
A-195773 / ABBOTT-195773 / ABT-773
International/Other Brands
Restanza
Categories
UNII
J0086219X6
CAS number
205110-48-1
Weight
Average: 765.945
Monoisotopic: 765.420045112
Chemical Formula
C42H59N3O10
InChI Key
PENDGIOBPJLVBT-AMXFZXBBSA-N
InChI
InChI=1S/C42H59N3O10/c1-11-32-42(8)36(44-40(50)55-42)25(4)33(46)23(2)21-41(7,51-18-14-15-28-20-29-16-12-13-17-30(29)43-22-28)37(26(5)34(47)27(6)38(49)53-32)54-39-35(48)31(45(9)10)19-24(3)52-39/h12-17,20,22-27,31-32,35-37,39,48H,11,18-19,21H2,1-10H3,(H,44,50)/t23-,24-,25+,26+,27-,31+,32-,35-,36-,37-,39+,41-,42-/m1/s1
IUPAC Name
(3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-2-hydroxy-3a,7,9,11,13,15-hexamethyl-11-{[3-(quinolin-3-yl)prop-2-en-1-yl]oxy}-3aH,4H,6H,7H,8H,9H,10H,11H,12H,13H,14H,15H,15aH-oxacyclotetradeca[4,3-d][1,3]oxazole-6,8,14-trione
SMILES
[H][[email protected]]12N=C(O)O[[email protected]]1(C)[[email protected]@]([H])(CC)OC(=O)[[email protected]]([H])(C)C(=O)[[email protected]]([H])(C)[[email protected]@]([H])(O[[email protected]]1([H])O[[email protected]]([H])(C)C[[email protected]]([H])(N(C)C)[[email protected]@]1([H])O)[[email protected]@](C)(C[[email protected]@]([H])(C)C(=O)[[email protected]]2([H])C)OCC=CC1=CC2=CC=CC=C2N=C1

Pharmacology

Indication

Investigated for use/treatment in bacterial infection, pediatric indications, and pneumonia.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Cethromycin is a ketolide antibiotic derived from erythromycin A with a 14 membered macrolide group. Its greater potency than macrolide antibiotics such as erythromycin, clrithromycin and azithromycin may be due to increased ribosomal binding affinity, increasing accumulation and decreasing efflux. Ketolide antibiotics lack the 3-O-cladinose (replaced by a keto group), a 11,12- or 6,11-cyclic moiety and a heteroaryl-alkyl side chain attached to the macrocyclic ring contained in macrolide antibiotics. They bind at two distinct binding sites in the 23S rRNA.

TargetActionsOrganism
U23S rRNANot AvailableEnteric bacteria and other eubacteria
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
Toxicity
Not Available
Affected organisms
  • Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cethromycin.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cethromycin.Approved
Food Interactions
Not Available

References

General References
  1. Van Bambeke F, Harms JM, Van Laethem Y, Tulkens PM: Ketolides: pharmacological profile and rational positioning in the treatment of respiratory tract infections. Expert Opin Pharmacother. 2008 Feb;9(2):267-83. doi: 10.1517/14656566.9.2.267 . [PubMed:18201149]
  2. Cao Z, Zhong P, Ruan X, Merta P, Capobianco JO, Flamm RK, Nilius AM: Ribosome affinity and the prolonged molecular postantibiotic effect of cethromycin (ABT-773) in Haemophilus influenzae. Int J Antimicrob Agents. 2004 Oct;24(4):362-8. [PubMed:15380262]
External Links
KEGG Drug
D02391
KEGG Compound
C12020
PubChem Compound
447451
PubChem Substance
310264871
ChemSpider
34991522
Wikipedia
Cethromycin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentPneumonia2

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00672 mg/mLALOGPS
logP4.84ALOGPS
logP4.41ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)3.69ChemAxon
pKa (Strongest Basic)7.68ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area166.31 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity205.37 m3·mol-1ChemAxon
Polarizability83.47 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Quinolines and derivatives / 1,3-dicarbonyl compounds / Benzenoids / Pyridines and derivatives / Oxazolidinones / Oxanes / Carbamate esters / Heteroaromatic compounds / 1,2-aminoalcohols / Trialkylamines
show 13 more
Substituents
Aminoglycoside core / Quinoline / Oxane / Oxazolidinone / Pyridine / Benzenoid / 1,3-dicarbonyl compound / Oxazolidine / Heteroaromatic compound / Carbamic acid ester
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

1. 23S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Unknown

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Katz DA, Grimm DR, Cassar SC, Gentile MC, Ye X, Rieser MJ, Gordon EF, Polzin JE, Gustavson LE, Driscoll RM, O'dea RF, Williams LA, Bukofzer S: CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels. Clin Pharmacol Ther. 2004 Jun;75(6):516-28. [PubMed:15179406]

Drug created on March 19, 2008 10:33 / Updated on November 09, 2017 03:54