Carfilzomib (PR-171) is an irreversible proteasome inhibitor with an IC₅₀ of 5 nM in ANBL-6 and RPMI 8226 cells.

IC50: 5 nM (Proteasome)

Carfilzomib displays preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM and above and little or no effect on the PGPH and T-L activities at doses up to 100 nM. Carfilzomib decreases the viability of ANBL-6, RPMI 8226 cells, U266 and KAS-6/1 cells with an IC₅₀ less than 5 nM. Carfilzomib overcome Dex resistance, in that MM1.R cells reveals an IC₅₀ of 15.2 nM, less than the value of 29.3 nM for parental MM1.S cells^[1]. Co-treatment with carfilzomib and HDACIs leads to synergistic induction of cell death in various mantle cell lymphoma lines and primary mantle cell lymphoma cells. Combined treatment with carfilzomib or ONX0912 with vorinostat in HF-4B and Granta cells sharply increases caspase activation, PARP cleavage, JNK activation, MnSOD2 induction, and DNA damage^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Carfilzomib (2.0 mg/kg, i.v.) in conbination with 70 mg/kg vorinostat virtually abrogates tumor growth in Granta-luciferace cell xenograft flank model. Combined treatment results in a pronounced reduction in bioluminescence compared to animals treated with single agents or controls with minimal toxicity^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

719.91

C₄₀H₅₇N₅O₇

868540-17-4

卡非佐米

Room temperature in continental US; may vary elsewhere.

*该产品在溶液状态不稳定，建议您现用现配，即刻使用。

DMF : ≥ 100 mg/mL (138.91 mM)

DMSO : 50 mg/mL (69.45 mM; Need ultrasonic)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现用现配，即刻使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (3.47 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (3.47 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.47 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• 3.

  请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

  Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic

• [1]. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90.

  [2]. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2011 Sep;10(9):1686-97.

WST-1 is used to determine the effects of proteasome inhibitors on cell proliferation according to the manufacturer’s protocol. The inhibition of proliferation is calculated in relation to parallel control cells that receive vehicle alone and tabulated in KaleidaGraph 3.0.1 or Excel 2000. 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).

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal studies are performed utilizing Beige-nude-XID mice. 10×10⁶ Granta514 cells are pelleted, washed twice with 1X PBS, injected subcutaneously into the right flank. Once the tumors are visible, 5 to 6 mice are treated with carfilzomib±vorinostat and progress of tumor growth or regression is monitored. Stock vorinostat and carfilzomib is dissolved in DMSO and 10% sulfobutylether betacyclodextrin in 10 mM citrate buffer pH respectively. They are stored in −80°C in small aliquots and diluted before injection.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90.

  [2]. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2011 Sep;10(9):1686-97.