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SNX-2112

现货
Catalog No.
A4068
ATP竞争性的强效Hsp90选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,800.00
现货
5mg
¥ 1,900.00
现货
10mg
¥ 2,600.00
现货
50mg
¥ 6,800.00
Ship with 10-15 days
100mg
¥ 9,800.00
Ship with 10-15 days

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Background

SNX-2112 is a potent inhibitor of synthetic heat shock protein (Hsp 90) with IC50 value of 30 nM.[1]
HSP90 (heat shock proteins) is widely expressed as a molecular chaperone. It plays an important role in the folding and stabilization of cellular proteins. HSP90 protects client proteins from degradation and maintains them in an active conformation. Many clientsof HSP90 are transcription factors or protein kinases such as: Bcr-Abl, tyrosine kinas, EGFR family members, IGF1-R, c-Met, steroid hormone receptors, p53, Mdm2 and telomerase. In a variety of cancers, overexpressed hsp90 has been detected. Hsp90 also play an important role in maintaining the transformed phenotype of cancer cell. So, Hsp 90 is one attractive target for cancer therapy.
SNX-2112 is a potent inhibitor of Hsp 90 in different cancer cell lines. In the MTT assay, SNX-2112 inhibited A-375 cells with IC50 values of 1.25 μM at 48h. In the western blot assay, 0.2 M SNX-2112 significantly reduced several growth-related Hsp90 client proteins such as Akt, p-Akt, IKKα, B-Raf, Erk1/2, p-Erk1/1, GSK3β and Chk1 in a time-dependent manner after 24h treatment. In the DAPI staining and the TUNEL assay, conclusive double-stranded DNA fragmentation were produced after exposure to 0.2μM SNX-2112.[2] Moreover, in the cell cycle assays, in 3 MET-amplified tumor cell lines (GTL-16, MKN-45 and EBC-1), 50nM SNX-2112 induced G1 arrest while in higher concentration such as 100 and 1000nM, more cells accumulated in G2 phase.[3] In pediatric cancer cell lines (SK-N-DZ, SK-N-AS, BE(2)-C, Saos-2, SK-N-SH, and U-2-OS ) SNX-2112 showed inhibition properties  at IC50 values ranging from 20-40 nM.[4]
References:
1.Chandarlapaty S, et al.SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin cancer Res(2008) 14(1): 240-248
2.Kai-Sheng Liu, et al. SNX-2112, an Hsp90 inhibitor, induces apoptosis and autophagy via degradation of Hsp90 client proteins in human melanoma A-375 cells. Cancer Letters. (2012) 318 180–188
3.Antitumor activity of SNX-2112, a synthetic heat shock protein-90 inhibitor, in MET-amplified tumor cells with or without resistance to selective MET inhibition. Clin Cancer Res. (2011) 17(1): 122–133
4.Daniel le C. Chin n,BS, et al. Anti-Tumor Activity of the HSP90 Inhibitor SNX-2112 in Pediatric Cancer Cell Lines. Pediatr Blood Cancer (2012)58:885–890

文献引用

1. Li QQ, Hao JJ,et al. "Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics." Sci Rep. 2017 Mar 15;7(1):201. PMID:28298630

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt464.48
Cas No.908112-43-6
FormulaC23H27F3N4O3
Solubility≥23.05 mg/mL in DMSO, ≥9.6 mg/mL in EtOH with ultrasonic and warming, <2.16 mg/mL in H2O
Chemical Name4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide
SDFDownload SDF
Canonical SMILESCC1(CC2=C(C(=O)C1)C(=NN2C3=CC(=C(C=C3)C(=O)N)NC4CCC(CC4)O)C(F)(F)F)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1-3]:

细胞系

无胸腺BALB/c雌性小鼠

溶解方法

该化合物在DMSO中的溶解度大于23.05 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

IC50: 10-50 nmol/L

应用

用SNX-2112(1 μmol/L)处理BT-474细胞,在药物暴露3-6 h内,HER2表达下降,处理10 h导致HER2表达近乎完全的丧失。在HER2过表达细胞中,SNX-2112诱导Hsp90客户蛋白降解,抑制Erk和Akt活化,并诱导细胞凋亡。在一组乳腺癌、肺癌和卵巢癌细胞系中,SNX-2112抑制细胞增殖,IC50值范围为10-50 nmol/L。在HER2扩增的BT-474乳腺癌细胞中,SNX-2112的抗增殖作用与Rb的超磷酸化、G1期停滞及凋亡水平适中有关。SNX-2112通过抑制Akt/mTOR/p70S6K以时间和剂量依赖的方式诱导自噬。SNX-2112诱导人黑色素瘤A-375细胞凋亡和自噬。SNX-2112(72h)诱导人慢性白血病K562细胞凋亡,IC50为0.92 μM。

动物实验 [3]:

动物模型

K562-NOD/SCID小鼠

给药剂量

6 mg/kg,第5-9天及12-16天尾静脉注射

应用

SNX-2112对接种K562细胞的NOD/SCID小鼠具有治疗作用。SNX-2112处理延长了接种K562细胞的NOD/SCID小鼠的存活时间。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Chandarlapaty S, Sawai A, Ye Q, et al. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase–dependent cancers[J]. Clinical Cancer Research, 2008, 14(1): 240-248.

[2]. Liu K S, Liu H, Qi J H, et al. SNX-2112, an Hsp90 inhibitor, induces apoptosis and autophagy via degradation of Hsp90 client proteins in human melanoma A-375 cells[J]. Cancer letters, 2012, 318(2): 180-188.

[3]. Jin L, Xiao C L, Lu C H, et al. Transcriptomic and proteomic approach to studying SNX‐2112‐induced K562 cells apoptosis and anti‐leukemia activity in K562‐NOD/SCID mice[J]. FEBS letters, 2009, 583(12): 1859-1866.

生物活性

描述 SNX-2112是Hsp90α和Hsp90β的ATP竞争性抑制剂,Ka值均为30 nM。
靶点 Hsp90α Hsp90β        
IC50 30 nM (Ka) 30 nM (Ka)        

质量控制

质量控制和MSDS

批次:

化学结构

SNX-2112

相关生物数据

SNX-2112