产品说明书

CB-5083

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Chemical Structure| 1542705-92-9 同义名 : -
CAS号 : 1542705-92-9
货号 : A287921
分子式 : C24H23N5O2
纯度 : 99%+
分子量 : 413.472
MDL号 : MFCD28963914
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(253.95 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：

0.5% CMC Na+5% Tween 80+water 30 mg/mL suspension

生物活性
靶点

  • ATPase

    p97 AAA ATPase, IC50:11 nM
描述 CB-5083 is a potent, ATP-competitive, D2-selective p97 inhibitor with IC50 value of 11nM against p97 ATPase activity. CB-5083 exhibited cell killing effect on >300 tumor cell lines tested with IC50 values ranging in 115-2000 nM, and poly-Ub accumulation in 12 tumor cell lines tested with IC50 values ranging in 150-800 nM. Oral administration of CB-5083 at dose of 75 mg/kg, qd, for 14 days suppressed tumor growth of Nu/Nu nude female mice bearing established human tumor xenografts derived from HCT 116 colon. Treatment with CB-5083 at a dose of 100 mg/kg on a qd4on/3off weekly schedule suppressed tumor growth in AMO-1 multiple myeloma model, which showed similar efficiency with bortezomib. However, bortezomib failed to suppress tumor growth in A549 lung carcinoma model, while CB-5083 showed potency to the same model. This suggested that CB-5083 could potentially be effective against both hematologic and solid tumors[1].
作用机制 CB-5083 is an ATP-competitive p97 inhibitor through specifically interacting with D2 site which is primarily responsible for the ATPase activity of p97.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.42mL

0.48mL

0.24mL

12.09mL

2.42mL

1.21mL

24.19mL

4.84mL

2.42mL
参考文献

[1]Zhou HJ, Wang J, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083). J Med Chem. 2015 Dec 24;58(24):9480-97.

[2]Anderson DJ, Le Moigne R, et al. Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis. Cancer Cell. 2015 Nov 9;28(5):653-665.