| AZ505 ditrifluoroacetateSMYD2 inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
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- View current batch:
- Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Kinase experiment [1]: | |
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]: | |
Cell | N/A |
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. |
Reaction Conditions | N/A |
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) |
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. | |
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| Cas No. | 1035227-44-1 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | 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 | ||
| Formula | C33H40Cl2F6N4O8 | M.Wt | 805.59 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
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.
