AZ505 ditrifluoroacetate
(Synonyms: N-环己基-3-[[2-(3,4-二氯苯基)乙基]氨基]-N-[2-[[2-(3,4-二氢-5-羟基-3-氧代-2H-1,4-苯并恶嗪-8-基)乙基]氨基]乙基]丙酰胺二(2,2,2-三氟乙酸盐)) 目录号 : GC13103
An inhibitor of SMYD2
Cas No.:1035227-44-1
Sample solution is provided at 25 µL, 10mM.
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AZ505 is a potent SET and MYND domain-containing 2 protein (SMYD2) inhibitor that selectively inhibits the enzymatic activity of SMYD2 (IC50: 0.12 μM) over a variety of other protein lysine methyltransferases (IC50 > 83.3 μΜ), including SMYD3, DOT1L, EZH2, GLP, G9A and SET7/9 [1].
AZ505 contains three distinct moieties: the benzooxazinone group which interacts with the lysine-binding channel of SMYD2; the cyclohexyl group which interacts with the core SET and I-SET domains of SMYD2; and the dichlorophenethyl group which extends across the peptide binding groove of SMYD2 [1].
The X-ray crystallographic analysis has revealed that AZ505 binds into the peptide binding groove of SMYD2 competing with the peptide substrates [1].
Reference
References:
[1] Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, Garcia-Arenas R, Cowen S, Wu J, Godin R, Chen H, Keen N. Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73. doi: 10.1016/j.str.2011.06.011. Epub 2011 Jul 21.
| Kinase experiment [1]: | |
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Inhibitory activities |
AZ505 binding to SMYD2 and inhibits SMYD2-mediated methylation in cells in the presence of SAM. In gastric cancer and ESCC, overexpression of SMYD2 protein was detected in 38.1% and 76.5% of patients, respectively. AZ505 inhibiting SMYD2 may be a key therapeutic strategy for these disease. |
| Cell experiment [1]: | |
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Cell |
N/A |
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Preparation method |
Soluble in DMSO. 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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Reaction Conditions |
N/A |
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Applications |
AZ505 inhibited SMYD2-mediated methylation in cells with IC50 value of 0.12 μM and AZ505 binding to SMYD2 is competitive with the peptide substrate and uncompetitive with the cofactor. AZ505 also inhibited other histone methyltransferases, such as SMYD3 (IC50>83.3 mM), DOT1L (IC50>83.3 mM) and EZH2 (IC50>83.3 mM) |
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References: [1] Ferguson AD, Larsen NA, Howard T, et dl. Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73. | |
| Cas No. | 1035227-44-1 | SDF | |
| 别名 | N-环己基-3-[[2-(3,4-二氯苯基)乙基]氨基]-N-[2-[[2-(3,4-二氢-5-羟基-3-氧代-2H-1,4-苯并恶嗪-8-基)乙基]氨基]乙基]丙酰胺二(2,2,2-三氟乙酸盐) | ||
| 化学名 | N-cyclohexyl-3-((3,4-dichlorophenethyl)amino)-N-(2-((2-(3,5-dihydroxy-2H-benzo[b][1,4]oxazin-8-yl)ethyl)amino)ethyl)propanamide bis(2,2,2-trifluoroacetate) | ||
| Canonical SMILES | ClC1=C(Cl)C=C(CCNCCC(N(C2CCCCC2)CCNCCC3=C4C(N=C(O)CO4)=C(O)C=C3)=O)C=C1.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O | ||
| 分子式 | C33H40Cl2F6N4O8 | 分子量 | 805.59 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store 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 | 1.2413 mL | 6.2066 mL | 12.4133 mL |
| 5 mM | 0.2483 mL | 1.2413 mL | 2.4827 mL |
| 10 mM | 0.1241 mL | 0.6207 mL | 1.2413 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet