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HA14-1

现货
Catalog No.
A8168
有效的、细胞通透的Bcl-2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
20mg
¥ 500.00
现货
50mg
¥ 1,100.00
现货
200mg
¥ 2,600.00
现货

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Background

HA14-1 is a potent small-molecule inhibitor of B-cell lymphoma 2 (Bcl-2), a protein factor binding to and inactivating pro-apoptotic proteins (such as Bax and BH3-only family proteins) to suppress apoptosis, that potently inhibits the anti-apoptotic of Bcl-2 and induces apoptosis with values of 50% inhibition concentration IC50 ranging from 10 to 20 μM in NIH3T3, HL60 and lung cancer H1299 cell lines. HA14-1 binds to Bcl-2 by mimicking the BH3 domain required for homo- and hetero-dimer formation and hence prevents the binding of these proteins subsequently resulting in the inhibition of Bcl-2. HA14-1 has been widely investigated in studies of apoptosis, which potentiates it to be used for the treatment of cancer.

Reference

Chen J, Freeman A, Liu J, Dai Q, Lee RM. The apoptotic effect of HA14-1, a Bcl-2-interacting small molecular compound, requires Bax translocation and is enhanced by PK11195. Mol Cancer Ther. 2002 Oct;1(12):961-7.

Niino S, Nakamura Y, Hirabayashi Y, Nagano-Ito M, Ichikawa S. A small molecule inhibitor of Bcl-2, HA14-1, also inhibits ceramide glucosyltransferase. Biochem Biophys Res Commun. 2013 Apr 5;433(2):170-4. doi: 10.1016/j.bbrc.2013.02.052. Epub 2013 Feb 26.

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt409.23
Cas No.65673-63-4
FormulaC17H17BrN2O5
Solubility≥20.45mg/mL in DMSO, ≥41.53 mg/mL in EtOH with ultrasonic, <2.77 mg/mL in H2O
Chemical Nameethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
SDFDownload SDF
Canonical SMILESCCOC(=O)C1=C(OC2=C(C1C(C#N)C(=O)OCC)C=C(C=C2)Br)N
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

HL-60细胞,滤泡淋巴瘤B细胞系,HF1A3,HF4.9和HF28RA细胞

溶解方法

该化合物在DMSO中的溶解度大于20.5 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

50 μM,4 h

应用

在HL-60细胞中,HA14-1以剂量依赖的方式诱导细胞死亡。HA14-1(50 μM)导致超过90%的细胞活力丧失。在HL-60细胞中,HA14-1(50μM)处理3小时诱导DNA断裂。在滤泡淋巴瘤B细胞系HF1A3、HF4.9和HF28RA细胞中,HA14-1降低细胞活力并诱导凋亡。HA14-1(10-20 μmol/L)增加人胶质母细胞瘤细胞对放疗诱导的凋亡和化疗诱导的细胞凋亡的敏感性。

动物实验 [3]:

动物模型

BeGBM细胞攻击的Swiss裸鼠

给药剂量

腹腔注射,400 nM,从第2天开始每周一次

应用

在用BeGBM细胞攻击的免疫缺陷Swiss裸鼠中,从第2天开始每周一次HA14-1(400 nmol)对胶质母细胞瘤肿瘤的生长没有显著影响。HA14-1(400 nM)增加了DNA损伤剂etoposide (2.5 mg/kg)对体内胶质母细胞瘤生长的影响。

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]. Wang J L, Liu D, Zhang Z J, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells[J]. Proceedings of the National Academy of Sciences, 2000, 97(13): 7124-7129.

[2]. Skommer J, Wlodkowic D, Mtt M, et al. HA14-1, a small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells[J]. Leukemia research, 2006, 30(3): 322-331.

[3]. Manero F, Gautier F, Gallenne T, et al. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death[J]. Cancer research, 2006, 66(5): 2757-2764.

生物活性

HA14-1是Bcl-2表面口袋的非肽配体,IC50值9 μM。M
靶点 Bcl-2          
IC50 9 μM          

质量控制

化学结构

HA14-1