HA14-1
(Synonyms: 乙基-2-氨基-6-溴-4-(1-氰基-2-乙氧基-2-甲酰)-4H-苯并呋喃-3-羧酸) 目录号 : GC11510
A Bcl-2 inhibitor
Cas No.:65673-63-4
Sample solution is provided at 25 µL, 10mM.
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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
[1].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.
[2].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.
| Cell experiment [1-3]: | |
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Cell lines |
HL-60 cells, follicular lymphoma B cell lines, HF1A3, HF4.9 and HF28RA cells |
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Preparation method |
The solubility of this compound in DMSO is >20.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
50 μM, 4 h |
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Applications |
In HL-60 cells, HA14-1 induced cell death in a dose-dependent manner. HA14-1 (50 μM) caused the loss of viability in more than 90% of the cells. In HL-60 cells, treatment with 50 μM HA14-1 by 3 h displayed the characteristic pattern of DNA fragmentation. HA14-1 decreased cell viability and induced apoptosis in follicular lymphoma B cell lines, HF1A3, HF4.9 and HF28RA cells. HA14-1 (10-20 μmol/L) increased sensitivity of human glioblastoma cells to radiotherapy-induced apoptosis and chemotherapy-induced apoptosis. |
| Animal experiment [3]: | |
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Animal models |
Swiss nude mice challenged with BeGBM cells |
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Dosage form |
Intraperitoneal injection, 400 nM, once weekly from day 2 |
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Application |
In Swiss nude mice challenged with BeGBM cells, HA14-1 (400 nmol, once weekly from day 2) did not have any significant effect on the growth of glioblastoma tumors in immunodeficient mice. HA14-1 (400 nM) increased the effect of the DNA-damaging agent etoposide (2.5 mg/kg) on glioblastoma growth in vivo. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 65673-63-4 | SDF | |
| 别名 | 乙基-2-氨基-6-溴-4-(1-氰基-2-乙氧基-2-甲酰)-4H-苯并呋喃-3-羧酸 | ||
| 化学名 | ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate | ||
| Canonical SMILES | CCOC(=O)C1=C(OC2=C(C1C(C#N)C(=O)OCC)C=C(C=C2)Br)N | ||
| 分子式 | C17H17BrN2O5 | 分子量 | 409.23 |
| 溶解度 | ≥ 20.45mg/mL in DMSO, ≥ 41.53 mg/mL in EtOH with ultrasonic | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4436 mL | 12.2181 mL | 24.4361 mL |
| 5 mM | 0.4887 mL | 2.4436 mL | 4.8872 mL |
| 10 mM | 0.2444 mL | 1.2218 mL | 2.4436 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet