Physicochemical Properties
| Molecular Formula | C50H88N28O15 |
| Molecular Weight | 1321.412 |
| Exact Mass | 766.314 |
| 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 | White solid |
| Boiling Point | 1376.7ºC at 760 mmHg |
| Flash Point | 786.4ºC |
| Vapour Pressure | 0mmHg at 25°C |
| Hydrogen Bond Donor Count | 27 |
| Hydrogen Bond Acceptor Count | 23 |
| Rotatable Bond Count | 19 |
| Heavy Atom Count | 93 |
| Complexity | 2470 |
| Defined Atom Stereocenter Count | 12 |
| 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) |
Biological Activity
| 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. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |