| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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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 |
| Molecular Formula |
C21H33F3N8O7
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|---|---|
| Molecular Weight |
566.531334638596
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| Exact Mass |
566.242
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| Elemental Analysis |
C, 44.52; H, 5.87; F, 10.06; N, 19.78; O, 19.77
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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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| PubChem CID |
134814505
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
39
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| Complexity |
700
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| Defined Atom Stereocenter Count |
5
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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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| InChi Key |
FZPZIBBKUWOBTJ-CPQMNCBCSA-N
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| InChi Code |
InChI=1S/C19H32N8O5.C2HF3O2/c1-25(2)5-3-6-26(7-4-11(20)19(30)31)8-12-14(28)15(29)18(32-12)27-10-24-13-16(21)22-9-23-17(13)27;3-2(4,5)1(6)7/h9-12,14-15,18,28-29H,3-8,20H2,1-2H3,(H,30,31)(H2,21,22,23);(H,6,7)/t11-,12+,14+,15+,18+;/m0./s1
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| Chemical Name |
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(dimethylamino)propyl]amino]butanoic acid;2,2,2-trifluoroacetic acid
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| Synonyms |
GSK2807 TFA; GSK2807 trifluoroacetic acid; GSK2807; GSK-2807; GSK 2807
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (176.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| 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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