| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
(1S,2S)-Bortezomib targets the 20S proteasome, the catalytic core of the ubiquitin-proteasome system responsible for degrading ubiquitinated proteins. The compound inhibits proteasome activity by binding to the threonine residue at the active site of the β5 subunit, which possesses chymotrypsin-like activity. This inhibition disrupts the cell cycle, induces apoptosis, and inhibits nuclear factor NF-κB signaling. The compound has also been observed to inhibit serine proteases and lower cellular Aβ concentrations, suggesting potential applications in Alzheimer's disease or hypertension research. The Ki of 0.6 nM indicates exceptionally high binding affinity for the proteasome.
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| ln Vitro |
In vitro, (1S,2S)-Bortezomib inhibits the 20S proteasome with a Ki of 0.6 nM, demonstrating potent and selective proteasome inhibition. The compound disrupts the cell cycle and induces apoptosis in various cancer cell lines through proteasome inhibition. It inhibits NF-κB signaling, which contributes to its anti-cancer effects. Cytotoxicity assays in A549 lung cancer and PC3 prostate cancer cell lines have confirmed the ability of Bortezomib and its analogs to induce cell death. The compound's reversible binding mechanism allows for controlled proteasome inhibition, distinguishing it from irreversible proteasome inhibitors.
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| ln Vivo |
(1S,2S)-Bortezomib, as the enantiomer of Bortezomib, exhibits in vivo anti-cancer activity through proteasome inhibition. Bortezomib causes a delay in tumor growth in nonclinical tumor models, including multiple myeloma xenografts. In vivo studies demonstrate that Bortezomib induces anti-cancer activity through multiple mechanisms of action. The compound is highly bound (≥80%) to plasma proteins. Studies in tumor-bearing RAG2⁻/⁻γc⁻/⁻ mice have evaluated Bortezomib concentrations and distribution in various organs over time. In vivo, Bortezomib delays tumor growth and enhances the cytotoxic effects of radiation and chemotherapy.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for (1S,2S)-Bortezomib typically involve proteasome activity assays using purified 20S proteasome complexes. The fluorogenic substrate Suc-LLVY-AMC (succinyl-leucine-leucine-valine-tyrosine-7-amino-4-methylcoumarin) is commonly used to measure chymotrypsin-like activity of the proteasome. The compound is incubated with purified 20S proteasome and substrate in assay buffer (typically 20 mM HEPES, pH 7.5, with appropriate salts). Fluorescence release from AMC cleavage is monitored over time (excitation 380 nm, emission 460 nm). IC₅₀ or Ki values are calculated from inhibition curves. This assay enables direct assessment of proteasome inhibition without cellular interference.
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| Cell Assay |
In vitro cellular experiments with (1S,2S)-Bortezomib are performed using various cancer cell lines including A549 (lung cancer), PC3 (prostate cancer), HepG2 (hepatocellular carcinoma), and multiple myeloma cell lines. Cells are seeded in appropriate culture media and treated with varying concentrations of the compound (typically 0.1-100 nM) for 24-48 hours. Cytotoxicity is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V-FITC/PI staining and flow cytometry. Proteasome inhibition is confirmed by accumulation of ubiquitinated proteins and proteasome substrates via Western blot analysis. Cells are cultured at 37°C in 5% CO₂ with appropriate media supplements.
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| Animal Protocol |
In vivo animal studies with Bortezomib have been extensively conducted in various tumor models. Multiple myeloma xenograft models in immunocompromised mice (such as RAG2⁻/⁻γc⁻/⁻ mice) are commonly used. Bortezomib is administered via intravenous injection at doses typically ranging from 0.5-1.0 mg/kg on a twice-weekly schedule. Tumor volume is measured by caliper twice weekly, and tumor growth inhibition is calculated relative to vehicle controls. Pharmacodynamic markers including proteasome inhibition in blood cells and tumor tissues are assessed. Bortezomib has been shown to delay tumor growth and enhance the effects of radiation and chemotherapy in these models.
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| ADME/Pharmacokinetics |
(1S,2S)-Bortezomib, as the enantiomer of Bortezomib, shares similar pharmacokinetic properties with the parent compound. Bortezomib is highly bound (≥80%) to plasma proteins. The compound is distributed throughout the body with concentrations decreasing over time in plasma and various organs. Bortezomib is metabolized primarily by cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19, and is eliminated via both hepatic and renal routes. The compound has a relatively short elimination half-life in humans, requiring twice-weekly dosing for therapeutic effect. Detailed PK parameters for the specific (1S,2S) enantiomer are extrapolated from the extensively characterized Bortezomib parent compound.
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| Toxicity/Toxicokinetics |
Toxicological information for (1S,2S)-Bortezomib is derived from the extensive safety profile of Bortezomib, the parent compound approved for clinical use. Bortezomib is associated with dose-limiting toxicities including peripheral neuropathy, thrombocytopenia, neutropenia, and gastrointestinal effects. The compound should be handled as a potent pharmaceutical ingredient with appropriate safety precautions. Hazard warnings include potential for serious eye damage and toxicity upon prolonged exposure. As an investigational compound, (1S,2S)-Bortezomib should be handled only by trained personnel using appropriate personal protective equipment in a well-ventilated area.
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| References |
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| Additional Infomation |
(1S,2S)-Bortezomib (CAS 1132709-14-8) is an enantiomer of Bortezomib, the first therapeutic proteasome inhibitor approved for human use in treating multiple myeloma and mantle cell lymphoma. The compound has molecular formula C₁₉H₂₅BN₄O₄ and molecular weight 384.24 g/mol. It appears as a white to off-white solid and is soluble in DMSO. Storage recommendations include -20°C for powder and -80°C for solutions. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB through proteasome inhibition. The (1S,2S) isomer is used in research to compare stereochemical effects on proteasome inhibition and is not approved for therapeutic use.
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| Molecular Formula |
C₁₉H₂₅BN₄O₄
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| Molecular Weight |
384.24
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| Exact Mass |
384.196
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| CAS # |
1132709-14-8
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| PubChem CID |
24871309
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Index of Refraction |
1.564
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| LogP |
2.45
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
28
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| Complexity |
500
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| Defined Atom Stereocenter Count |
2
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| SMILES |
B([C@@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O
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| InChi Key |
GXJABQQUPOEUTA-DOTOQJQBSA-N
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| InChi Code |
InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17+/m0/s1
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| Chemical Name |
[(1S)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid
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| Synonyms |
(1S,2S)Bortezomib (1S,2S) Bortezomib
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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 : ~50 mg/mL (~130.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.51 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 (6.51 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 (6.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6025 mL | 13.0127 mL | 26.0254 mL | |
| 5 mM | 0.5205 mL | 2.6025 mL | 5.2051 mL | |
| 10 mM | 0.2603 mL | 1.3013 mL | 2.6025 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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