| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| Targets |
Aminoglycoside
|
|---|---|
| ln Vitro |
The cyclic peptide antibiotics capreomycin and viomycin are generally effective against the bacterial pathogen Mycobacterium tuberculosis. However, recent virulent isolates have become resistant by inactivation of their tlyA gene. We show here that tlyA encodes a 2'-O-methyltransferase that modifies nucleotide C1409 in helix 44 of 16S rRNA and nucleotide C1920 in helix 69 of 23S rRNA. Loss of these previously unidentified rRNA methylations confers resistance to capreomycin and viomycin. Many bacterial genera including enterobacteria lack a tlyA gene and the ensuing methylations and are less susceptible than mycobacteria to capreomycin and viomycin. We show that expression of recombinant tlyA in Escherichia coli markedly increases susceptibility to these drugs. When the ribosomal subunits associate during translation, the two tlyA-encoded methylations are brought into close proximity at interbridge B2a. The location of these methylations indicates the binding site and inhibitory mechanism of capreomycin and viomycin at the ribosome subunit interface[3].
|
| ln Vivo |
Capreomycin (1.4, 7.2 and 14.5 mg/kg inhaled; 20 mg/kg IM; 4 weeks) lowers wet lung weight and reduces bacterial load in sick guinea pig lungs [2].
|
| Enzyme Assay |
M. tuberculosis wild-type Beijing D3 and rrl mutant C-401 were inoculated in triplicate into 7H9 media without drug and 7H9 media containing 10 μg/ml capreomycin and were grown at 37°C for 21 days. Growth of the cultures was monitored daily at OD600. The MICs of antibiotics were determined for each strain as previously described (Maus et al., 2005a, Maus et al., 2005b).[3]
Overnight cultures of E. coli cells were diluted 105-fold and plated onto Lauria-Bertani agar (Sambrook et al., 1989) containing viomycin, capreomycin, kanamycin, or rifampicin with concentrations increasing in 2-fold steps. The agar plates were incubated at 37°C, and MICs were scored as the lowest concentration at which no growth was observed.[3]
|
| Animal Protocol |
Animal/Disease Models: Male guinea pig [836±162.3g; 2 × 105 CFU/mL Mycobacterium tuberculosis (strain H37Rv) via respiratory nebulization suspension][2]
Doses: Inhalation 1.4, 7.2 and 14.5 mg/kg; 20 mg /kg for intramuscular Route of Administration: inhalation or intramuscularinjection; 4-week Experimental Results: At the dose of 14.5 mg/kg, the lung wet weight was Dramatically diminished, which was less than that of the 1.4 mg/kg group and the control group. The bacterial load in the lungs was Dramatically diminished at 14.5 mg/kg (3.52 ± 0.20 CFU/mL) compared with the control (4.58 ± 0.20 CFU/mL) and 1.4 and 7.2 mg/kg (4.02 ± 0.32 and 4.01 ± 0.29); P < 0.05) CFU/mL) respectively. |
| References |
[1]. Maus CE, et al. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005 Feb;49(2):571-7.
[2]. Garcia-Contreras L, et al. Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model. Antimicrob Agents Chemother. 2007 Aug;51(8):2830-6. [3]. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173-82. |
| Molecular Formula |
C50H88N28O15
|
|---|---|
| Molecular Weight |
1321.412
|
| Exact Mass |
766.31402
|
| Elemental Analysis |
C, 45.45; H, 6.71; N, 29.68; O, 18.16
|
| CAS # |
11003-38-6
|
| Related CAS # |
Capreomycin sulfate;1405-37-4
|
| PubChem CID |
484211591
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| Boiling Point |
1376.7ºC at 760 mmHg
|
| Flash Point |
786.4ºC
|
| Vapour Pressure |
0mmHg at 25°C
|
| tPSA |
480.83
|
| SMILES |
O=C1[C@]([H])([C@@]2([H])CCN=C(N)N2)NC(/C(=C\NC(N)=O)/NC([C@H](CNC(C[C@H](CCCN)N)=O)NC([C@H](CO)NC([C@H](CN1)N)=O)=O)=O)=O.O=C1[C@]([H])([C@@]2([H])CCN=C(N)N2)NC(/C(=C\NC(N)=O)/NC([C@H](CNC(C[C@H](CCCN)N)=O)NC([C@H](C)NC([C@H](CN1)N)=O)=O)=O)=O
|
| InChi Key |
VCOPTHOUUNAYKQ-WBTCAYNUSA-N
|
| InChi Code |
InChI=1S/C25H44N14O8.C25H44N14O7/c26-4-1-2-11(27)6-17(41)32-8-14-20(43)35-15(9-34-25(30)47)21(44)39-18(13-3-5-31-24(29)38-13)23(46)33-7-12(28)19(42)37-16(10-40)22(45)36-14;1-11-19(41)36-15(9-32-17(40)7-12(27)3-2-5-26)21(43)37-16(10-34-25(30)46)22(44)39-18(14-4-6-31-24(29)38-14)23(45)33-8-13(28)20(42)35-11/h9,11-14,16,18,40H,1-8,10,26-28H2,(H,32,41)(H,33,46)(H,35,43)(H,36,45)(H,37,42)(H,39,44)(H3,29,31,38)(H3,30,34,47);10-15,18H,2-9,26-28H2,1H3,(H,32,40)(H,33,45)(H,35,42)(H,36,41)(H,37,43)(H,39,44)(H3,29,31,38)(H3,30,34,46)/b15-9+;16-10+/t11-,12-,13+,14-,16-,18-;11-,12-,13-,14+,15-,18-/m00/s1
SMILES Code: C[C@@H]1NC([C@H](CNC([C@H]([C@H]2CCN=C(N2)N)NC(/C(NC([C@@H](NC1=O)CNC(C[C@H](CCCN)N)=O)=O)=C\NC(N)=O)=O)=O)N)=O.NCCC[C@@H](CC(NC[C@@H]3NC([C@@H](NC([C@H](CNC([C@H]([C@H]4CCN=C(N4)N)NC(/C(NC3=O)=C\NC(N)=O)=O)=O)N)=O)CO)=O)=O)N
|
| Chemical Name |
(S)-3,6-diamino-N-(((2S,5S,11S,15S,E)-15-amino-11-((R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl)-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-8-(ureidomethylene)-1,4,7,10,13-pentaazacyclohexadecan-5-yl)methyl)hexanamide compound with (S)-3,6-diamino-N-(((2S,5S,11S,15S,E)-15-amino-11-((R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl)-2-methyl-3,6,9,12,16-pentaoxo-8-(ureidomethylene)-1,4,7,10,13-pentaazacyclohexadecan-5-yl)methyl)hexanamide (1:1)
|
| Synonyms |
HSDB-3211; HSDB3211; HSDB 3211
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7568 mL | 3.7838 mL | 7.5677 mL | |
| 5 mM | 0.1514 mL | 0.7568 mL | 1.5135 mL | |
| 10 mM | 0.0757 mL | 0.3784 mL | 0.7568 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.
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