Product Data?SheetCarfilzomibCat. No.:CAS No.:分?式:分?量:作?靶点:作?通路:储存?式:HY-10455868540-17-4C??H??N?O?719.91Proteasome; Autophagy; ApoptosisMetabolic Enzyme/Protease; Autophagy; ApoptosisPowder-20°C4°C3 years2 yearsInhibitors?Agonists?Screening Libraries* 该产品在溶液状态不稳定，建议您现?现配，即刻使?。溶解性数据体外实验DMF : ≥ 100 mg/mL (138.91 mM)DMSO : 50 mg/mL (69.45 mM; Need ultrasonic)H2O : < 0.1 mg/mL (insoluble)* \Mass1 mg5 mg10 mgSolventConcentration制备储备液1 mM5 mM10 mM1.3891 mL0.2778 mL0.1389 mL6.9453 mL1.3891 mL0.6945 mL13.8906 mL2.7781 mL1.3891 mL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?现配， 即刻使?.体内实验请根据您的实验动物和给药?式选择适当的溶解?案。以下溶解?案都请先按照 In Vitro ?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?作液，建议您现?现配，当天使?； 以下溶剂前显?的百分?是指该溶剂在您配制终溶液中的体积占?；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?式助溶1. 请依序添加每种溶剂：?10% DMSO ?? 40% PEG300 ?? 5% Tween-80 ?? 45% salineSolubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic此?案可获得 2.5 mg/mL (3.47 mM) 的均匀悬浊液，悬浊液可?于?服和腹腔注射。 以 1 mL ?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? 50 μL Tween-80，混合均匀；然后继续加? 450 μL ?理盐?定容? 1 mL。2. 请依序添加每种溶剂：?10% DMSO ?? 90% corn oilSolubility: ≥ 2.5 mg/mL (3.47 mM); Clear solutionPage 1 of 2 www.MedChemExpress.cn
此?案可获得 ≥ 2.5 mg/mL (3.47 mM，饱和度未知) 的澄清溶液，此?案不适?于实验周期在半个?以上的实验。 以 1 mL ?作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL ??油中，混合均匀。
BIOLOGICAL ACTIVITY
?物活性IC?? & Target体外研究
Carfilzomib是不可逆的蛋?酶体 (proteasome) 抑制剂，其在ANBL-6和RPMI 8226细胞中的 IC50 为5 nM。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].
体内研究
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].
PROTOCOL
Cell Assay [1]
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
Administration [2]
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.
客户使?本产品发表的科研?献
????Elife.?2019 Mar 25;8. pii: e45457.
????Mol Cancer Ther. 2017 Dec;16(12):2862-2870.
????Mol Cell Proteomics. 2017 Apr;16(4 suppl 1):S144-S160.????Biochem Pharmacol. 2018 Oct;156:511-523.
Page 2 of 3 www.MedChemExpress.cn
????J Agric Food Chem. 2017 Jun 7;65(22):4384-4394.See more customer validations on www.MedChemExpress.cnREFERENCES
[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.
McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.
Tel: 400-820-3792; 021-58955995 Fax: 021-53700325 E-mail: tech@MedChemExpress.cn
Master of Small Molecules — 您?边的抑制剂?师
Page 3 of 3 www.MedChemExpress.cn
相关推荐：
loading