Disease relevance of RU66647

• In order to identify the ketolide-binding site on the ribosome, a library of Escherichia coli clones, transformed with a plasmid carrying randomly mutagenized rRNA operon, was screened for mutants exhibiting resistance to the ketolide HMR3647 [1].
• In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae [2].
• In vitro development of resistance to telithromycin (HMR 3647), four macrolides, clindamycin, and pristinamycin in Streptococcus pneumoniae [3].
• In vitro activities of ketolides HMR 3647 [correction of HRM 3647] and HMR 3004 [correction of HRM 3004], levofloxacin, and other quinolones and macrolides against Neisseria spp. and Moraxella catarrhalis [4].
• Telithromycin (HMR 3647) is a new ketolide that belongs to a new class of semisynthetic 14-membered-ring macrolides which have expanded activity against multidrug-resistant gram-positive bacteria [5].

High impact information on RU66647

• Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections [6].
• Pharmacokinetics of the new ketolide telithromycin (HMR 3647) administered in ascending single and multiple doses [7].
• TNF-alpha and GM-CSF (but not the other cytokines) decreased the inhibitory effect of HMR 3647 only on oxidant production by PMN [8].
• Roxithromycin and two ketolides, HMR 3647 and HMR 3004, were chosen as the test agents [8].
• We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E(max) model [9].

Chemical compound and disease context of RU66647

• HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae [10].

Biological context of RU66647

• HMR 3647 displayed Michaelis-Menten saturation kinetics with a mean Vmax of 2315 ng/2.5 x 10(6) PMNs/5 min and a mean Km of 117 mg/liter (144 microM) [11].
• Telithromycin (HMR 3647) had an IC50 = 0.08 microg/ml, and HMR 3832 was least effective with an IC50 = 0.11 microg/ml [12].

Anatomical context of RU66647

• Interactions between HMR 3647, a new ketolide, and human polymorphonuclear neutrophils [11].
• About 60% of HMR 3647 was located in the granular compartment; less than 6% was associated with the membranes [11].
• HMR 3647 is effective against L. pneumophila in vitro, in infected macrophages, and in a guinea pig model of Legionnaires' disease [13].
• Since macrolides have been shown to accumulate in human polymorphonuclear cells (PMNs), we have investigated the ability of the molecule HMR3647 to enter human PMNs as well as other cell types, such as peripheral blood mononuclear cells and cell lines of hematopoietic and nonhematopoietic origin [14].
• Telithromycin (HMR 3647) achieves high and sustained concentrations in tonsils of patients undergoing tonsillectomy [15].

Associations of RU66647 with other chemical compounds

• E. faecalis strains that had erythromycin MICs of 128 to > 512 micrograms/ml showed HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml [16].
• In vitro activities of ketolide HMR 3647, macrolides, and clindamycin against Coryneform bacteria [17].
• All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 micrograms/ml [16].

Gene context of RU66647

• Several ketolides are described here, including ABT 773 and telithromycin (HMR 3647), both of which possess a carbamate at C11/C12 of the macrolactone ring [18].

Analytical, diagnostic and therapeutic context of RU66647

• After incubation with the radiolabelled drug, HMR 3647 uptake was determined by a velocity gradient centrifugation technique [11].
• The comparative in vitro activity of HMR 3004 and HMR 3647, new ketolide antibiotics, was tested by a standard agar dilution technique against 221 pneumococcal strains, including isolates with intermediate levels of resistance to penicillin and erythromycin-resistant isolates [19].
• HMR 3647 appears to be a very promising agent for the treatment of respiratory infections and is currently in clinical trials [20].

References