AZ505 ditrifluoroacetate
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.
| Storage | Store at -20°C |
| M.Wt | 805.59 |
| Cas No. | 1035227-44-1 |
| Formula | C33H40Cl2F6N4O8 |
| Solubility | insoluble in H2O; ≥119.8 mg/mL in DMSO; ≥7.3 mg/mL in EtOH with ultrasonic |
| 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) |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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. |
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Quality Control & MSDS
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Chemical structure
