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| Other Sizes |
| Targets |
Bortezomib-d8 targets the same 20S proteasome as the parent drug bortezomib. It is a reversible and selective inhibitor of the chymotrypsin-like activity of the 26S proteasome, which is crucial for protein degradation. This inhibition disrupts multiple signaling pathways, leading to cell cycle arrest and apoptosis in cancer cells. As an internal standard, it is used to accurately measure levels of bortezomib in research.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Bortezomib-d8 is not typically used to assess biological activity in vitro, as it is an analytical standard. The parent compound, bortezomib, demonstrates potent in vitro activity against various cancer cell lines, including multiple myeloma, by inducing G2-M cell cycle arrest and apoptosis. Its proteasome inhibition activity is often measured using IC50 values against the chymotrypsin-like site, typically in the low nanomolar range. |
| ln Vivo |
Bortezomib-d8 is not used to study biological efficacy in vivo, as it is a stable isotope-labeled compound. For the parent drug, in vivo activity is well-documented, showing significant tumor growth inhibition in xenograft models of human cancer. However, as an internal standard, Bortezomib-d8 is administered to animals to study the pharmacokinetics and tissue distribution of the unlabeled drug via LC-MS/MS methods.
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| Enzyme Assay |
Bortezomib-d8 is used as an internal standard in non-cellular methods, primarily LC-MS/MS. The assay involves adding a known amount of Bortezomib-d8 to a biological sample (e.g., plasma or cell lysate). Following protein precipitation and liquid-liquid extraction, the extract is analyzed via HPLC-MS/MS. The compound is then used to correct for analyte recovery and matrix effects by comparing the signal of bortezomib to the signal of Bortezomib-d8.
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| Cell Assay |
Cell-based assays for Bortezomib-d8 are not performed for efficacy, but rather for analytical purposes. For stability studies, multiple myeloma cells are spiked with bortezomib and incubated. After a defined period, Bortezomib-d8 is added, and the intracellular concentration of the parent drug is determined via LC-MS/MS. This process allows researchers to quantify the amount of bortezomib that has been taken up by the cells and assess its degradation.
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| Animal Protocol |
In vivo studies using Bortezomib-d8 involve its administration to rodents (mice or rats). The compound is typically spiked into plasma samples as an internal standard before extraction. For the parent drug, a typical protocol involves administering bortezomib via intravenous injection. Blood samples are collected at various time points, centrifuged to obtain plasma, and stored at -80degC until LC-MS/MS analysis with Bortezomib-d8.
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| ADME/Pharmacokinetics |
Bortezomib-d8 is used specifically as an internal standard in pharmacokinetic studies. A validated UPLC-MS/MS method using Bortezomib-d8 showed excellent linearity over a range of 0.5-2500 pg per sample. In human plasma, an LC-MS/MS method demonstrated high accuracy (within +/-15% of nominal concentration) and precision (≤15% CV) with a recovery rate of approximately 83%. As a deuterated compound, it has a distinct molecular weight (+8 Da) for accurate MS detection.
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| Toxicity/Toxicokinetics |
Bortezomib-d8 is used as an analytical reference standard, and its direct toxicological profile is not extensively reported. The parent drug bortezomib is known to have significant toxicities, including peripheral neuropathy, thrombocytopenia, and neutropenia. As a research-use chemical, Bortezomib-d8 should be handled with appropriate laboratory safety practices, including the use of personal protective equipment.
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| References |
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| Additional Infomation |
Bortezomib-d8 has a molecular formula of C19H17D8BN4O4 and a molecular weight of 392.29 g/mol. It is a deuterium-labeled (d8) isotopologue of bortezomib (PS-341, LDP-341). The compound is a reversible and selective inhibitor of the 20S proteasome, clinically approved for treating multiple myeloma and mantle cell lymphoma. This stable isotope-labeled form is for research use only and is not intended for human therapy.
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| Molecular Formula |
C19H17D8BN4O4
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| Molecular Weight |
392.29
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| Related CAS # |
Bortezomib;179324-69-7
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| Appearance |
Typically exists as solid at room temperature
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5491 mL | 12.7457 mL | 25.4913 mL | |
| 5 mM | 0.5098 mL | 2.5491 mL | 5.0983 mL | |
| 10 mM | 0.2549 mL | 1.2746 mL | 2.5491 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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