UNC0638
目录号 : GC15610
A G9a and GLP histone methyltransferase inhibitor
Cas No.:1255580-76-7
Sample solution is provided at 25 µL, 10mM.
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UNC0638 is a potent and selective inhibitor of G9a and GLP with IC50 values of < 15 nM and 19 ± 1 nM, respectively [1].
GLP forms a heterodimer with G9a. Both G9a and GLP can mono- and dimethylate histone H3 Lys9 (H3K9), and dimethylate Lys373 of p53 and hence inactivate the transcriptional activity of p53 [1].
UNC0638 showed balanced physicochemical properties and potency aiding cell penetration in vitro, had high potency in cellular assays. It was much less toxic than BIX01294 to cells. In MDA-MB-231 cells, in a concentration-dependent manner, exposure to UNC0638 for 48 h reduced H3K9me2 levels with an IC50 value of 81 ± 9 nM (n= 3), which showed considerably higher potency than BIX01294 (IC50= 500 ± 43 nM (n= 3)). In reducing H3K9me2 levels, UNC0638 was of greater maximum effect than BIX01294. This effect is close, but not equal, to the effect on the double knockdown of G9a and GLP via shRNA [1].
In 6-week-old male athymic nude mice subcutaneously inoculated with BON cells, UNC0638 decreased H3K9me2 level [2]. In organotypic cochlear cultures, rapid increase of H3K9me2 upon the damage of hair cells was observed. Both ex vivo and in vivo, UNC0638 effectively prevented aminoglycosides-induced hair cell damage [3].
References:
[1]. Vedadi M., Barsyte-Lovejoy D., Liu F., et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nature Chemical Biology, 2011, 7:566-574.
[2]. Kim J.T., Li J., Jang E.R., et al. Deregulation of Wnt/β-catenin signaling through genetic or epigenetic alterations in human neuroendocrine tumors. Clin. Carcinogenesis, 2013, 00(00):1-9.
[3]. Yu H., Lin Q., Wang Y., et al. Inhibition of H3K9 methyltransferases G9a/GLP prevents ototoxicity and ongoing hair cell death. Cell Death and Disease, 2013, 4:e506.
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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 |
80, 250, 500 nM; 1 d to 4 d |
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Applications |
In MDA-MB-231 cells, in a concentration-dependent manner, exposure to UNC0638 for 48 h reduced H3K9me2 levels with an IC50 value of 81 ± 9 nM. Cellular levels of H3K9me2 were progressively reduced from 1 d to 4 d exposure to UNC0638 at the concentrations of 80 nM (IC50), 250 nM (IC90) and 500 nM (2 × IC90). The reductions of H3K9me2 levels with 250 nM and 500 nM treatments after 4 d were equal or very close to that of G9a and GLP knockdown cells. The effects of UNC0638 were long-lasting. In cells with 2 d exposure to UNC0638, levels of H3K9me2 remained low after washout of compound followed by 2 d incubation without the inhibitor. |
| Animal experiment [2]: | |
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Animal models |
Swiss Albino mice |
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Dosage form |
5 mg/kg; i.p. |
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Applications |
UNC0638 was not suitable for animal studies due to its poor pharmacokinetic properties. |
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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]. Vedadi M., Barsyte-Lovejoy D., Liu F., et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nature Chemical Biology, 2011, 7:566-574. [2]. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013 Nov 14;56(21):8931-42. | |
| Cas No. | 1255580-76-7 | SDF | |
| 化学名 | 2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine | ||
| Canonical SMILES | CC(C)N1CCC(CC1)NC2=NC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)C5CCCCC5 | ||
| 分子式 | C30H47N5O2 | 分子量 | 509.72 |
| 溶解度 | ≥ 25.5mg/mL 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 | 1.9619 mL | 9.8093 mL | 19.6186 mL |
| 5 mM | 0.3924 mL | 1.9619 mL | 3.9237 mL |
| 10 mM | 0.1962 mL | 0.9809 mL | 1.9619 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