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Purity: ≥98%
GSK2807 TFA (GSK-2807 TFA), the trifluoroacetic acid salt form of GSK2807, is a selective and SAM-competitive SMYD3 inhibitor with potential antitumor activity. It inhibits SMYD3 with a Ki of 14 nM. SMYD3 is a lysine methyltransferase overexpressed in colorectal, breast, prostate, and hepatocellular tumors, and has been implicated as an oncogene in human malignancies. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers. Structural and kinetic characterization of SMYD3 was undertaken leading to a co-crystal structure of SMYD3 with a MEKK2-peptide substrate bound, and the observation that SMYD3 follows a partially processive mechanism. These insights allowed for the design of GSK2807, a potent and selective, SAM-competitive inhibitor of SMYD3 (Ki = 14 nM). A high-resolution crystal structure reveals that GSK2807 bridges the gap between the SAM-binding pocket and the substrate lysine tunnel of SMYD3. Taken together, the data demonstrate that small-molecule inhibitors of SMYD3 can be designed to prevent methylation of MEKK2 and these could have potential use as anticancer therapeutics.
| ln Vitro |
GSK2807 fills the space between SMYD3's substrate lysine tunnel and SAM binding pocket, according to the high-resolution crystal structure. Compared to the similarly related enzyme SMYD2, GSK2807 exhibits a 24 times greater selectivity for SMYD3 (Ki 14±6 nM vs. 345±36 nM, respectively) [1].
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| References |
[1]. Van Aller GS, et al. Structure-Based Design of a Novel SMYD3 Inhibitor that Bridges the SAM-and MEKK2-Binding Pockets. Structure. 2016 May 3;24(5):774-781.
[2]. Kaniskan HÜ, et al. Inhibitors of Protein Methyltransferases and Demethylases. Chem Rev. 2018 Feb 14;118(3):989-1068. |
| Molecular Formula |
C21H33F3N8O7
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|---|---|
| Molecular Weight |
566.531334638596
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| CAS # |
2245255-66-5
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| Related CAS # |
2245255-66-5 (TFA);2245255-65-4;
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| SMILES |
FC(C(=O)O)(F)F.O1[C@H]([C@@H]([C@@H]([C@H]1CN(CC[C@@H](C(=O)O)N)CCCN(C)C)O)O)N1C=NC2C(N)=NC=NC1=2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~176.51 mM)
H2O : ≥ 50 mg/mL (~88.26 mM) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7651 mL | 8.8257 mL | 17.6513 mL | |
| 5 mM | 0.3530 mL | 1.7651 mL | 3.5303 mL | |
| 10 mM | 0.1765 mL | 0.8826 mL | 1.7651 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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