| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
The molecular target of Daptomycin-D-Asn-d5 TFA is the same as Daptomycin. Daptomycin targets the bacterial cell membrane of Gram-positive bacteria. It binds to phosphatidylglycerol (PG) in the membrane in a calcium-dependent manner. This binding causes the insertion of the lipophilic tail into the membrane, leading to the formation of a channel or ion pore. This disrupts the membrane potential, leading to rapid depolarization, inhibition of DNA, RNA, and protein synthesis, and ultimately cell death. The D-Asn-d5 labeling does not alter the mechanism; the compound is a stable isotope tracer.
|
|---|---|
| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
The deuterated Daptomycin-D-Asn-d5 TFA has the same in vitro bactericidal activity as the parent Daptomycin. Daptomycin is rapidly bactericidal against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae. The minimum inhibitory concentration (MIC) for susceptible strains is typically ≤1 ug/mL. It exhibits concentration-dependent killing. The deuterated version is not typically used in bioactivity assays; it is an internal standard for quantification. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
In vivo, Daptomycin is indicated for the treatment of complicated skin and skin structure infections (cSSSI), bacteremia, and right-sided infective endocarditis caused by S. aureus. Daptomycin-D-Asn-d5 TFA is not administered in vivo; it is an analytical standard. It is used in preclinical pharmacokinetic studies to measure the concentration of daptomycin in plasma and tissues. The deuterated compound offers advantages in mass spectrometry by acting as a tracer for quantitation during the drug development process. It corrects for matrix effects and extraction recovery. |
| Enzyme Assay |
Not applicable. Daptomycin-D-Asn-d5 TFA is an analytical standard, not a test compound for enzyme assays. For quality control, the compound is characterized by its purity (>98%), mass spectrometry (MS) profile, and NMR. The molecular weight of the labeled compound (1967.77 Da) is determined by high-resolution mass spectrometry (HRMS). The TFA counterion content is measured. The degree of deuteration (>99%) is confirmed. No biological assays are performed on the standard.
|
| Cell Assay |
Daptomycin-D-Asn-d5 TFA is not used in cell-based assays. For toxicity screening, the unlabeled Daptomycin is used. The labeled standard is used in LC-MS/MS method development. For the quantification of Daptomycin in human plasma, 50 uL of plasma is spiked with 10 uL of Daptomycin-D-Asn-d5 TFA (internal standard, 100 ng/mL). The sample is extracted by protein precipitation with acetonitrile. The supernatant is injected onto a C18 reverse-phase column. The mobile phase is water/acetonitrile with 0.1% formic acid. Detection is performed in positive ion mode using multiple reaction monitoring (MRM) transition m/z 811.4 → 341.2 (for Daptomycin) and m/z 816.4 → 346.2 (for the internal standard).
|
| Animal Protocol |
No in vivo animal protocol for Daptomycin-D-Asn-d5 TFA exists, as it is an internal standard. For pharmacokinetic studies of Daptomycin, male CD-1 mice (6-8 weeks old, n=6/group) are administered a single intravenous (IV) dose of daptomycin (20-50 mg/kg). Blood samples are collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24 h post-dose. The labeled standard is added to each plasma sample before extraction to quantify the concentration of unlabeled daptomycin by LC-MS/MS. PK parameters (Cmax, Tmax, AUC, t½, CL, Vd) are calculated by non-compartmental analysis.
|
| ADME/Pharmacokinetics |
Not applicable. Daptomycin-D-Asn-d5 TFA is an analytical standard, not a drug. It is not intended for in vivo use. The unlabeled Daptomycin has a plasma half-life of approximately 7-8 hours in humans. It is not metabolized by CYP450 enzymes; it is eliminated renally. The deuterated compound is stored as a solid at -20degC. It is soluble in DMSO and water. The TFA salt is used to improve solubility and stability. The compound is a controlled substance.
|
| Toxicity/Toxicokinetics |
For Daptomycin-D-Asn-d5 TFA, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). For research use only. The TFA salt is corrosive.
|
| References | |
| Additional Infomation |
Not applicable.
|
| Molecular Formula |
C78H99D5F9N17O32
|
|---|---|
| Molecular Weight |
1967.77
|
| Related CAS # |
Daptomycin; 103060-53-3
|
| Appearance |
Solid powder
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 0.5082 mL | 2.5409 mL | 5.0819 mL | |
| 5 mM | 0.1016 mL | 0.5082 mL | 1.0164 mL | |
| 10 mM | 0.0508 mL | 0.2541 mL | 0.5082 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
