SNX-2112
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SNX-2112是合成的热休克蛋白(Hsp 90)的强效抑制剂,IC50值为30 nM[1]。
Hsp90(热休克蛋白)作为一种分子伴侣,被广泛地表达。它在细胞蛋白折叠和稳定化中起重要作用。Hsp90使受体蛋白免受降解,并保持它们的活性构象。许多Hsp90受体蛋白是转录因子或蛋白激酶,如:Bcr-Abl、酪氨酸激酶、EGFR家族成员、IGF1-R、c-Met、类固醇激素受体、p53、Mdm2和端粒酶。在各种癌症中,检测到过度表达的Hsp90。Hsp90在维持癌细胞的转化表型方面也发挥着重要的作用。所以,Hsp90是一个很有吸引力的癌症治疗靶点。
SNX-2112是不同癌细胞株中Hsp90的强效抑制剂。在MTT试验中,SNX-2112在48 h时抑制A-375细胞,IC50值为1.25 μM。在免疫印迹试验中,0.2 M SNX-2112在处理后的第24 h起,时间依赖性地显著减少几种生长相关的Hsp90受体蛋白,如:Akt、p-Akt、IKKα、B-Raf、Erk1/2、p-ERK1/1、GSK3β和Chk1。在DAPI染色和TUNEL试验中,经0.2 μM SNX-2112处理后,产生双链DNA片段[2]。此外,在细胞周期试验中,在3种MET基因扩增的肿瘤细胞系(GTL-16,MKN-45和EBC-1)中,50 nM的SNX-2112诱导G1期阻滞,而在较高浓度,如:100和1000 nM,更多的细胞集中在G2期[3]。在儿科肿瘤细胞系(SK-N-DZ、SK- N- AS、BE(2)-C、Saos-2、SK-N-SH和U-2-OS)中,SNX-2112具有抑制活性,IC50值为20~40 nM[4]。
参考文献:
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
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 464.48 |
Cas No. | 908112-43-6 |
Formula | C23H27F3N4O3 |
Solubility | ≥23.05 mg/mL in DMSO; insoluble in H2O; ≥9.6 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide |
SDF | Download SDF |
Canonical SMILES | CC1(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 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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) |