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Carfilzomib

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Chemical Structure| 868540-17-4 同义名 : PR-171
CAS号 : 868540-17-4
货号 : A101004
分子式 : C40H57N5O7
纯度 : 98%
分子量 : 719.91
MDL号 : MFCD11040997
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(166.69 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 3 mg/mL clear

PO 0.5% CMC-Na 20 mg/mL suspension

生物活性
靶点

  • Proteasome

    Proteasome, IC50:5 nM
描述 The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. Proteasome Subunit β5 is a component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. Proteasome Subunit β5 displays a chymotrypsin-like activity. Carfilzomib is a proteasome inhibitor, specifically inhibiting the chymotrypsin-like (ChT-L) activity at the β5 subunits of the core 20S proteasome[3]. According to a report, extracts from multiple myeloma ANBL-6 cells were exposed to increasing concentrations of carfilzomib and assayed for 20S catalytic activities. Carfilzomib displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at the dose of 10 nM and little or no effect on the PGPH and T-L activities at doses up to 100 nM. In an ELISA assay utilizing cell extracts from ANBL-6 cells, designed to identify subunit binding, short exposure to Carfilzomib at the concentration as low as 0.1 μM exhibited preferential binding specificity for the β5 constitutive 20S proteasome. Based on a WST-1 assay, the inhibitory IC50s of Carfilzomib against multiple myeloma ANBL-6 and RPMI8226 cells were both less than 5 nM, with the drug incubation time of 24h. In a caspase activity assay, ANBL-6 cells were exposed to a 1-hour pulse of 100 nM Carfilzomib and allowed to recover for 8 hours. The results indicated that Carfilzomib increased caspase-3 activity approximately 6-fold, and caspase-8, caspase-9 activity approximately 4-fold[4]. In a mouse model of bone marrow disseminated multiple myeloma established by intravenous injection of 5TGM1-GFP cells into KaLwRij mice, Carfilzomib was intravenously administrated at the dose of 3 mg/kg daily for 2 days. The treatment of Carfilzomib significantly decreased tumor burden as measured by serum levels of the clonotypic antibody IgG2b and by percentage of bone marrow or spleen GFP-expressing tumor cells. Protection from tumor-induced bone loss was also observed by microCT[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
1483 200 nM Apoptosis Asssay 24 h induce the cell apoptosis co-treatment with ONX 0912 22929803
1483 Growth Inhibition Assay IC50=50.5 ± 11.9 nM 22929803
Cal33 Growth Inhibition Assay IC50=49.3 ± 8.9 nM 22929803
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.95mL

1.39mL

0.69mL

13.89mL

2.78mL

1.39mL
参考文献

[1]Kuhn DJ, Orlowski RZ, Bjorklund CC. Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs). Curr Cancer Drug Targets. 2011 Mar;11(3):285-95. doi: 10.2174/156800911794519725. PMID: 21247387.

[2]Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ. 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. doi: 10.1182/blood-2007-01-065888. Epub 2007 Jun 25. PMID: 17591945; PMCID: PMC2200918.

[3]Hurchla MA, Garcia-Gomez A, Hornick MC, Ocio EM, Li A, Blanco JF, Collins L, Kirk CJ, Piwnica-Worms D, Vij R, Tomasson MH, Pandiella A, San Miguel JF, Garayoa M, Weilbaecher KN. The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia. 2013 Feb;27(2):430-40. doi: 10.1038/leu.2012.183. Epub 2012 Jul 5. PMID: 22763387; PMCID: PMC3771507.