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TMP269

现货
Catalog No.
A8806
HDAC4/5/7/9抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,800.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,800.00
现货

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Background

TMP269 is a novel and selective inhibitor of class IIa histone deacetylase with IC50 values of 126, 80, 36, 9 nM for HDAC 4, 5, 7, 9, respectively [1].

Histone deacetylases (HADC) are a series of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone and make the histones to wrap the DNA more tightly, which prevent transcription.

TMP269 is a novel and selective class IIa HDAC inhibitor. In MM cell lines, TMP269 induced modest cytotoxicity with IC50 values ranging from 22 to 38 μM in a dose-dependent way, which was associated with cleavage of caspase-3, -8, -9 and PARP. Also, TMP269 enhanced CFZ-induced apoptosis and increased the expression of activating transcription factor 4 (ATF4) and proapoptotic transcription factor C/EBP homologous protein (CHOP). In the presence of BMSCs or IL-6, TMP269 and CFZ also showed significant cytotoxicity [2]. In IEC-18 intestinal epithelial cells, TMP269 inhibited cell proliferation, cell cycle progression and DNA synthesis in response to G protein-coupled receptor/protein kinase D1 (PKD1) activation [3].

References:
[1].  Lobera M, Madauss KP, Pohlhaus DT, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol, 2013, 9(5): 319-325.
[2].  Kikuchi S, Suzuki R, Ohguchi H, et al. Class IIa HDAC inhibition enhances ER stress-mediated cell death in multiple myeloma. Leukemia, 2015.
[3].  Sinnett-Smith J, Ni Y, Wang J, et al. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling. Am J Physiol Cell Physiol, 2014, 306(10): C961-71.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt514.52
Cas No.1314890-29-3
FormulaC25H21F3N4O3S
SynonymsTMP 269;TMP-269
Solubility≥23mg/mL in DMSO
Chemical Name(Z)-N-((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)-3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzimidic acid
SDFDownload SDF
Canonical SMILESFC(F)(F)C1=NC(C2=CC(/C(O)=N/CC3(C4=NC(C5=CC=CC=C5)=CS4)CCOCC3)=CC=C2)=NO1
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]:

细胞系

IEC-18细胞

溶解方法

该化合物在DMSO中的溶解度大于23 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

4 μM, 18 h, 37°C

应用

在IEC-18肠上皮细胞中,TMP269有效抑制ANG II诱导的[3H]胸苷掺入,EC50大约为1.5 μM。TMP269完全防止了ANG II刺激的G0/G1到G2/M转变。

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]. Sinnett-Smith J, Ni Y, Wang J, et al. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling[J]. American Journal of Physiology-Cell Physiology, 2014, 306(10): C961-C971.

生物活性

描述 TMP269是一种有效的和选择性的IIa类HDAC抑制剂,作用于HDAC4、HDAC5、HDAC7和HDAC9,IC50值分别为157 nM、97 nM、43 nM和23 nM。
靶点 HDAC9 HDAC7 HDAC5 HDAC4    
IC50 23 nM 43 nM 97 nM 157 nM    

质量控制

质量控制和MSDS

批次:

化学结构

TMP269