UNC0638 |
| カタログ番号GC15610 |
G9aとGLPヒストンメチルトランスフェラーゼ阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | 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 | ||
| Formula | C30H47N5O2 | M.Wt | 509.72 |
| 溶解度 | ≥ 25.5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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