Onalespib

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Chemical Structure| 912999-49-6 同义名 : AT13387
CAS号 : 912999-49-6
货号 : A389427
分子式 : C24H31N3O3
纯度 : 99%+
分子量 : 409.52
MDL号 : MFCD18633198
存储条件：

Pure form Inert atmosphere, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

2% DMSO+30% PEG 300+water 10 mg/mL

生物活性
描述 HSP90 (heat shock protein 90) is a cellular ubiquitous molecular chaperone responsible for promoting the conformational mutation and stabilization of several client oncoproteins, including Met, B-Raf, p53, Akt, and Kit, function of which is required by tumor cells to maintain appropriate client protein expression necessary for proliferation and survival. Onalespib is a potent HSP90 inhibitor with Kd value of 0.71nM. Treatment with Onalespib led to the down-regulation of the oncogenic client proteins Raf-1 and CDK4 at concentration around 30nM, as well as growth inhibition with IC50 value of 48nM in HCT116 cells. The up-regulation of Hsp70 can be observed at concentration>10nM, which was regarded as a biomarker readout for Hsp90 inhibition. Intraperitoneal injection with the L-lactate salt form of Onalespib at dose of 60mg/kg per day for 3 days on and 3 days off for four cycles caused tumor growth inhibition by 78% in HCT116nhuman colon cancer xenografts and a tumor growth delay of 17 days after cessation of dosing[1].
作用机制 Onalespib can bind in the ATPase binding site of HSP90.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
human A231 cells Proliferation assay 48 h Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=1.01 μM 24763261
human HCT116 cells Cytotoxic assay Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.048 μM 20662534
human HCT116 cells Proliferation assay 48 h Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=0.08 μM 24763261
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.21mL

2.44mL

1.22mL

24.42mL

4.88mL

2.44mL
参考文献

[1]Courtin A, Smyth T, et al. Emergence of resistance to tyrosine kinase inhibitors in non-small-cell lung cancer can be delayed by an upfront combination with the HSP90 inhibitor onalespib. Br J Cancer. 2016 Oct 25;115(9):1069-1077.

[2]Graham B, Curry J, et al. The heat shock protein 90 inhibitor, AT13387, displays a long duration of action in vitro and in vivo in non-small cell lung cancer. Cancer Sci. 2012 Mar;103(3):522-7.

[3]Canella A, Welker AM, et al. Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas. Clin Cancer Res. 2017 Oct 15;23(20):6215-6226.