SNX-2112

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Chemical Structure| 908112-43-6 同义名 : PF-04928473
CAS号 : 908112-43-6
货号 : A371641
分子式 : C23H27F3N4O3
纯度 : 99%+
分子量 : 464.48
MDL号 : MFCD16038907
存储条件:

Pure form Keep in dark place, 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:

0.5% CMC+0.25% Tween 80+water 30 mg/mL suspension

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. SNX-2112 and its prodrug SNX-5422 are HSP90 inhibitors with IC50 value of 30nM (measured by ATP displacement assay). Treatment with SNX-2112 led to downregulation of protein level of HER2 and AKT signaling, in a time-dependent (at 1μM with 48h) and dose-dependent (<1μM for 24h) in BT-474 cells. SNX-2112 inhibited cell proliferation of a panel of breast, lung, and ovarian cancer cell lines with IC50 values ranging in 10-50nM, and also caused a profound mitotic block in MDA-468 cells at 1μM for 48h. Consistent with apoptosis induced by SNX-2112, increased cleaved PARP and decreased CDK1 can also be observed in BT-474 cells treated with SNX-2112. A single dose of 50m/kg SNX-2112 can repeat the effect on the client protein in vivo, with most potency at 10h post dose. Oral administration of SNX-2112 at dose of 50mg/kg, 5 days per week, could significantly inhibit tumor growth in BT474 tumor xenografts after treatment for 4 weeks, and in H1650 tumor xenografts after treatment for 37 days[1].
作用机制 SNX-2112 binds to the amino-terminal ATP 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
A375 cells Function assay 24 h Inhibition of Hsp90 in human A375 cells assessed as pS6 degradation after 24 hrs by high content screening, IC50=0.001 μM 19552433
AU565 cells Function assay 24 h Inhibition of Hsp90 in human AU565 cells assessed as pERK degradation after 24 hrs by high content screening, IC50=0.041 μM 19552433
HCT15 cells Proliferation assay 72-144 h Antiproliferative activity against human HCT15 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.052 μM 19552433
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.22mL

10.76mL

2.15mL

1.08mL

21.53mL

4.31mL

2.15mL

参考文献

[1]Chandarlapaty S, Sawai A, et al. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8.

[2]Dong D, Wang X, et al. Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112. Int J Nanomedicine. 2015 Mar 31;10:2521-35.