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Purity: ≥98%
Telithromycin (also known as HMR-3647; HMR3647; RU66647; RU-66647) is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treat community acquired pneumonia of mild to moderate severity. After significant safety concerns, the US Food and Drug Administration sharply curtailed the approved uses of the drug in early 2007. Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting a ketogroup for the cladinose sugar and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the carbon at position 6 has been methylated, as is the case in clarithromycin, to achieve better acid-stability.
Targets |
Macrolide
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ln Vitro |
Telithromycin (HMR3647) (0-50 μg/mL, 30 min) inhibits the production of MUC5AC induced by C. pneumoniae.The NF-kB activation caused by C. pneumoniae is suppressed by telithromycin (0-50 μg/mL, 30 min)[1].
LPS-stimulated RAW 264.7 macrophages produce less MIP-2 and TNF-α when exposed to telithromycin (10 mg/mL, 1 h) in a dose-dependent manner.Telithromycin (10 mg/mL, 1 h) reduces the LPS-induced neutrophil influx in BAL fluid, increases apoptosis in cells, and inhibits NF-kB activation[2]. |
ln Vivo |
In the BAL fluid of animals nebulized with LPS, telithromycin (HMR3647) (20 mg/kg, ip., single) decreases the levels of protein, nitrite, MIP-2, and TNF-α[2].
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Enzyme Assay |
MUC5AC production in bronchial epithelial cells after stimulation with C. pneumoniae was analyzed by ELISA and quantitative RT-PCR. NF-kappaB and phosphorylated ERK were also analyzed. For inhibition study, cells were pretreated with azithromycin, clarithromycin and telithromycin before stimulation.[1]
C. pneumoniae dose-dependently induced MUC5AC production and gene expression. The ERK-NF-kappaB pathway was involved in C. pneumoniae-induced MUC5AC production. Macrolides and ketolides dose-dependently reduced C. pneumoniae-induced MUC5AC production. However, azithromycin was apparently less effective than the other antibiotics. Clarithromycin and telithromycin, but not azithromycin, reduced NF-kappaB activation.[1] |
Cell Assay |
We measured the effects of TEL on the response of RAW 264.7 macrophages to LPS and of murine lung epithelial (MLE)-12 cells to supernatants of LPS-stimulated RAW 264.7 macrophages. Macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-alpha production, nuclear factor (NF)-kappaB activation, and apoptosis were determined. Acute airway inflammation was induced in untreated and TEL-treated BALB/c mice by nebulization with LPS. Total number of leukocytes, macrophages, and neutrophils, the protein concentration, and nitrite and cytokine levels were determined in the BAL fluid.[2]
TEL inhibited in a dose-dependent manner the production of MIP-2 and TNF-alpha by LPS-stimulated RAW 264.7 macrophages, and the production of MIP-2 by MLE-12 epithelial cells to supernatants of LPS-stimulated RAW 264.7 macrophages. NF-kappaB activation was inhibited and apoptosis was increased in both cell lines by TEL. The LPS-induced influx of neutrophils in BAL fluid was decreased by TEL pretreatment. [2] |
Animal Protocol |
Animal Model: LPS-Nebulized Mice[2]
Dosage: 20 mg/kg Administration: 20 mg/kg, ip., single Result: induced significant reductions in MIP-2 levels, decreased TNF-α and nitrite concentrations, and increased protein concentration. |
References |
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Additional Infomation |
The ketolide antibiotic telithromycin (TEL) exerts immunomodulatory and antiinflammatory effects in vitro and in a mouse model of septic shock. We studied the antiinflammatory activity of TEL in in vitro and in vivo models of airway inflammation induced by lipopolysaccharide (LPS).[2]
Airway mucus hypersecretion is an important problem in chronic respiratory diseases including bronchial asthma. Chlamydophila pneumoniae is recently confirmed to be a pathogen in bronchial asthma, but the relationship between C. pneumoniae and mucus hypersecretion is uncertain. In this study, we examined whether C. pneumoniae induces MUC5AC mucin in airway epithelial cells. We also examined the effects of macrolide and ketolide antibiotics on the C. pneumoniae-induced mucus production.[1] |
Molecular Formula |
C43H65N5O10
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Molecular Weight |
812.003700000001
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Exact Mass |
811.47
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Elemental Analysis |
C, 63.60; H, 8.07; N, 8.62; O, 19.70
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CAS # |
191114-48-4
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PubChem CID |
3002190
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Appearance |
White to off-white solid powder
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Density |
1.3±0.1 g/cm3
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Boiling Point |
966.2±65.0 °C at 760 mmHg
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Melting Point |
176-188ºC
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Flash Point |
538.2±34.3 °C
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Vapour Pressure |
0.0±0.3 mmHg at 25°C
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Index of Refraction |
1.589
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LogP |
4.52
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tPSA |
171.85
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SMILES |
O=C([C@H](C)C[C@@](C)(OC)[C@H](O[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O)[C@@H](C)C([C@@H](C)C(O[C@H](CC)[C@@]2(C)O3)=O)=O)[C@H](C)[C@@]2([H])N(CCCCN4C=C(C5=CC=CN=C5)N=C4)C3=O
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InChi Key |
LJVAJPDWBABPEJ-PNUFFHFMSA-N
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InChi Code |
InChI=1S/C43H65N5O10/c1-12-33-43(8)37(48(41(53)58-43)19-14-13-18-47-23-31(45-24-47)30-16-15-17-44-22-30)27(4)34(49)25(2)21-42(7,54-11)38(28(5)35(50)29(6)39(52)56-33)57-40-36(51)32(46(9)10)20-26(3)55-40/h15-17,22-29,32-33,36-38,40,51H,12-14,18-21H2,1-11H3/t25-,26-,27+,28+,29-,32+,33-,36-,37-,38-,40+,42-,43-/m1/s1
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Chemical Name |
(3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-10-(((2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-(4-(4-(pyridin-3-yl)-1H-imidazol-1-yl)butyl)octahydro-2H-[1]oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(1H,7H,9H)-tetraone
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Synonyms |
HMR3647; RU-66647; RU 66647; RU66647;HMR-3647; HMR 3647;
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~100 mg/mL (~123.15 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.08 mM) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.2315 mL | 6.1576 mL | 12.3153 mL | |
5 mM | 0.2463 mL | 1.2315 mL | 2.4631 mL | |
10 mM | 0.1232 mL | 0.6158 mL | 1.2315 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.