Carfilzomib (PR-171)

製品コードS2853 バッチS285308

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C40H57N5O7
分子量 719.91 CAS No. 868540-17-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (138.9 mM)
Ethanol 50 mg/mL (69.45 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
2%DMSO 30%PEG300 2%TWEEN80 66%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 1.000mg/ml (1.39mM) Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

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.
in vitro

Carfilzomib (PR-171) 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). It reveals enhanced anti-MM activity, overcome resistance to other agents, and acts synergistically with (Dex). This compound 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 it 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, it has also shown preclinical effectiveness against hematological and solid malignancies. [2] This compound directly inhibits osteoclasts formation and bone resorption. [3]
in vivo

Carfilzomib (PR-171) moderately reduces tumor growth in an in vivo xenograft model, effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking, 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
ANBL-6 cells (2 × 106/well) are plated in 96-well plates and treated with Carfilzomib (PR-171) 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 of this compound 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 Carfilzomib (PR-171), a proteasome inhibitor, 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 of this compound 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.
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

  • https://pubmed.ncbi.nlm.nih.gov/17591945/
  • https://pubmed.ncbi.nlm.nih.gov/21247387/
  • https://pubmed.ncbi.nlm.nih.gov/22763387/
  • https://pubmed.ncbi.nlm.nih.gov/21750224/

カスタマーフィードバック

Data from [Data independently produced by Sci Transl Med, 2014, 6(250), 250ra112]

Data from [Cancer Res, 2014, 74(16), 4458-69]

Data from [J Virol, 2013, 87(23), 13035-41]

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Oversized cells activate global proteasome-mediated protein degradation to maintain cell size homeostasis [ Elife, 2025, 14e75393] PubMed: 39791360
Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax [ J Transl Med, 2025, 23(1):917] PubMed: 40814067
Integrated real-time imaging of executioner caspase dynamics, apoptosis-induced proliferation, and immunogenic cell death using a stable fluorescent reporter platform [ Cell Death Discov, 2025, 11(1):368] PubMed: 40769969
Carfilzomib-specific proteasome β5/β2 inhibition drives cardiotoxicity via remodeling of protein homeostasis and the renin-angiotensin-system [ iScience, 2025, 28(9):113228] PubMed: 40894880
Inhibitors of the ubiquitin‑proteasome system rescue cellular levels and ion transport function of pathogenic pendrin (SLC26A4) protein variants [ Int J Mol Med, 2025, 55(5)69] PubMed: 40052591

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。

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