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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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LLY-507 (LLY507) is a novel, potent, cell-permeable/active and selective inhibitor of protein-lysine methyltransferase SMYD2 (SET And MYND Domain Containing 2) with potential anticancer activity. It inhibits SMYD2 with an IC50 of 15 nM. SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys(370) at submicromolar concentrations. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes.
| ln Vitro |
LLY-507 targets over twenty-one other methyltransferases, including SMYD3 in addition to SMYD2[1]. LLY-507 supports SMYD2's inhibitory action by binding to its substrate channel [1]. SMYD2 LLY-507 (0.03 – 20 μM; 28 hours) inhibits p53 Lys370 methylation mediated by SMYD2 in U2OS cells (IC50 0.6 μM[1]); enzyme methylation of H4 peptide (IC50 31 nM[1]). The growth of several ESCC, HCC, and breast cancer cell lines is inhibited by LLY-507 (0–20 μM; 3-7) [1].
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: ESCC, HCC, breast cancer cell line Tested Concentrations:0-20 μM Incubation Duration: 3 days, 7 days Experimental Results: Inhibit tumor cell proliferation. Western Blot Analysis[1] Cell Types: HEK293 Cell Tested Concentrations: 0.03 μM, 0.07 μM, 0.15 μM, 0.3 μM, 0.6 μM, 1.25 μM, 2.5 μM Incubation Duration: 28 hrs (hours) Experimental Results: Inhibition of SMYD2-mediated p53 Lys370 alpha in cells base. |
| References | |
| Additional Infomation |
LLY-507 is a secondary carboxamide resulting from the formal condensation of the carboxy group of 5-cyano-2'-{4-[2-(3-methyl-1H-indol-1-yl)ethyl]piperazin-1-yl}[biphenyl]-3-carboxylic acid with the amino group of 3-(pyrrolidin-1-yl)propan-1-amine. It is a potent and selective inhibitor of SMYD2 and inhibits the ability of SMYD2 to methylate p53. It serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes. It has a role as an EC 2.1.1.354 ([histone H3]-lysine(4) N-trimethyltransferase) inhibitor. It is a methylindole, a N-alkylpiperazine, a N-arylpiperazine, a nitrile, a member of benzamides, a secondary carboxamide and a N-alkylpyrrolidine.
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| Molecular Formula |
C36H42N6O
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|---|---|
| Molecular Weight |
574.758287906647
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| Exact Mass |
574.341
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| CAS # |
1793053-37-8
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| PubChem CID |
91623361
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
790.4±70.0 °C at 760 mmHg
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| Flash Point |
431.8±35.7 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
7.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
43
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| Complexity |
935
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PNYRDVBFYVDJJI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H42N6O/c1-28-27-42(34-11-4-2-9-32(28)34)22-19-40-17-20-41(21-18-40)35-12-5-3-10-33(35)30-23-29(26-37)24-31(25-30)36(43)38-13-8-16-39-14-6-7-15-39/h2-5,9-12,23-25,27H,6-8,13-22H2,1H3,(H,38,43)
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| Chemical Name |
3-cyano-5-[2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide
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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 |
| 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 : ~15 mg/mL (~26.10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.35 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7399 mL | 8.6993 mL | 17.3986 mL | |
| 5 mM | 0.3480 mL | 1.7399 mL | 3.4797 mL | |
| 10 mM | 0.1740 mL | 0.8699 mL | 1.7399 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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