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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C40H57N5O7 |
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| 分子量 | 719.91 | CAS No. | 868540-17-4 | |
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (138.9 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis. |
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| in vitro | Carfilzomib inhibits proliferation in a variety of cell lines and patient-derived neoplastic cells, including multiple myeloma, and induced intrinsic and extrinsic apoptotic signaling pathways and activation of c-Jun-N-terminal kinase (JNK). Carfilzomib reveals enhanced anti-MM activity compared with bortezomib, overcome resistance to bortezomib and other agents, and acts synergistically with dexamethasone (Dex). Carfilzomib shoes preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM. Short exposure to low-dose Carfilzomib leads to preferential binding specificity for the β5 constitutive 20S proteasome and the β5i immunoproteasome subunits. Measurement of caspase activity in ANBL-6 cells pulsed with Carfilzomib reveals substantial increases in caspase-8, caspase-9, and caspase-3 activity after 8 hours, giving a 3.2-, 3.9- and 6.9-fold increase, respectively, over control cells after 8 hours. In carfilzomib pulse-treated cells, the mitochondrial membrane integrity is decreased to 41% (Q1 + Q2), compared with 75% in vehicle-treated control cells. [1] In another study, Carfilzomib has also shown preclinical effectiveness against hematological and solid malignancies. [2] Carfilzomib directly inhibits osteoclasts formation and bone resorption. [3] |
| in vivo | Carfilzomib moderately reduces tumor growth in an in vivo xenograft model. Carfilzomib effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking. Carfilzomib increases trabecular bone volume, decreases bone resorption and enhances bone formation in non-tumor bearing mice. [3] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Enzyme-linked immunosorbent assay for subunit profiling of carfilzomib | |
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| ANBL-6 cells (2 × 106/well) are plated in 96-well plates and treated with Carfilzomib doses from 0.001 to 10 μM for 1 hour. Cells are then lysed (20 mM Tris-HCl, 0.5 mM EDTA), and cleared lysates are transferred to polymerase chain reaction (PCR) plates. A standard curve is generated using untreated ANBL-6 cell lysates starting at a concentration of 6 μg protein/μL. The active site probe [biotin-(CH2)4-Leu-Leu-Leu-epoxyketone; 20 μM] is added and incubated at room temperature for 1 hour. Cell lysates are then denatured by adding 1% sodium dodecyl sulfate (SDS) and heating to 100°C, followed by mixing with 20 μL per well streptavidin-sepharose high-performance beads in a 96-well multiscreen DV plate and incubated for 1 hour. These beads are then washed with enzyme-linked immunosorbent assay (ELISA) buffer (PBS, 1% bovine serum albumin, and 0.1% Tween-20), and incubated overnight at 4°C on a plate shaker with antibodies to proteasome subunits. Antibodies used included mouse monoclonal anti-β1, anti-β2, anti-β1i, and anti-β5i, goat polyclonal anti-β2i, and rabbit polyclonal anti-β5 (affinity-purified antiserum against KLH-CWIRVSSDNVADLHDKYS peptide). The beads are washed and incubated for 2 hours with horseradish peroxidase-conjugated secondary goat antirabbit, goat antimouse or rabbit antigoat antibodies. After washing, the beads are developed using the supersignal ELISA picochemiluminescence substrate. Luminescent detection is performed. Raw luminescence is converted to μg/mL by comparison with the standard curve and expressed as the % inhibition relative to vehicle control. Curve fits are generated using the following nonsigmoidal dose-response equation: Y = Bottom + (Top-Bottom)/(1 + 10̂((LogEC50 − X) × HillSlope)), where X is the logarithm of concentration, Y is the % inhibition, and EC50 is the dose showing 50% effect. | ||
| 細胞アッセイ | 細胞株 | WST-1, ANBL-6 cells |
| 濃度 | 100 nM | |
| 反応時間 | 1 hour | |
| 実験の流れ | WST-1 is used to determine the effects of proteasome inhibitor Carfilzomib on cell proliferation. The inhibition of proliferation is calculated in relation to parallel control cells that receives vehicle alone. A linear spline function is used to interpolate the median inhibitory concentration (IC50) using XLfit 4 software. The degree of resistance (DOR) is calculated using the formula: DOR = IC50(resistant cells)/IC50(sensitive cells). ANBL-6 cells pulsed with 100 nM carfilzomib are washed and suspended in PBS containing 5 μg/mL of JC-1, which exhibits potential-dependent accumulation in mitochondria. Analysis of the mitochondrial membrane potential-dependent color shift from 525 to 590 nm is carried out on a FacScan, and the data are analyzed with CellQuest software. |
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| 動物実験 | 動物モデル | Beige-nude-XID mice |
| 投薬量 | 2.0 mg/kg | |
| 投与方法 | i.v. | |
参考
カスタマーフィードバック
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Data from [Data independently produced by Sci Transl Med, 2014, 6(250), 250ra112]
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Data from [Cancer Res, 2014, 74(16), 4458-69]
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Data from [J Virol, 2013, 87(23), 13035-41]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins [ Nat Commun, 2024, 15(1):2485] | PubMed: 38509117 |
| MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis [ J Exp Clin Cancer Res, 2024, 43(1):68] | PubMed: 38439082 |
| Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity [ J Transl Med, 2024, 22(1):208] | PubMed: 38413989 |
| A small-molecule degrader selectively inhibits the growth of ALK-rearranged lung cancer with ceritinib resistance [ iScience, 2024, 27(2):109015.] | PubMed: 38327793 |
| BRD4-targeting PROTAC as a unique tool to study biomolecular condensates [ Cell Discov, 2023, 9(1):47] | PubMed: 37156794 |
| Combinations of ivermectin with proteasome inhibitors induce synergistic lethality in multiple myeloma [ Cancer Lett, 2023, 565:216218] | PubMed: 37149018 |
| Mutations in the B30.2 and the central helical scaffold domains of pyrin differentially affect inflammasome activation [ Cell Death Dis, 2023, 14(3):213] | PubMed: 36966139 |
| Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells [ Cell Death Dis, 2023, 14(1):42] | PubMed: 36658130 |
| FAM193A is a positive regulator of p53 activity [ Cell Rep, 2023, 42(3):112230] | PubMed: 36897777 |
| The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma [ Blood Adv, 2023, 7(14):3485-3500] | PubMed: 36920785 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。