LLY-507 potently inhibits the ability of SMYD2 to methylate p53 peptide with an IC50 <15 nM. LLY-507 is able to potently inhibit the methylation of H4 peptide by SMYD2 enzyme with an IC50 of 31 nM. It has 100-fold selectivity for SMYD2 over 24 other protein or DNA methyltransferases including related family members SMYD3, SUVH420H1, and SUV420H2. LLY-507 inactives (>20 μM) against 454 kinases, 35 G protein-coupled receptors, 14 nuclear hormone receptors, and three cytochrome P450 enzymes. LLY-507 inhibits the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner.
| Cell Experiment | |
|---|---|
| Cell lines | HEK293 cells |
| Preparation method | To examine the methylation status of p53 in HEK293 cells treated with LLY-507 by Western blotting, 2 × 105 cells are seeded in 6-well plates in triplicate and co-transfected with FLAG-tagged p53 and FLAG-tagged SMYD2 using Lipofectamine® 2000. The day after transfection, cells are treated with 0-2.5 μM LLY-507 for 28 h, then collected, and lysed in radioimmunoprecipitation assay (RIPA) buffer. Cell lysates are subject to 10% SDS-PAGE and transferred to a PVDF membrane. |
| Concentrations | 0-2.5 μM |
| Incubation time | 28 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 574.76 |
| Formula | C36H42N6O |
| CAS Number | 1793053-37-8 |
| Solubility (25°C) | 100 mg/mL in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Histone Methyltransferase Products |
|---|
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SAH-EZH2, a stable EZH2 α-helical peptide, is an EZH2/EED interaction inhibitor. |
| UNC4976
UNC4976 is a positive allosteric modulator (PAM) peptidomimetic of CBX7 chromodomain binding to nucleic acids. |
| C21
C21 is a potent, irreversible, and selective PRMT1 inhibitor with an IC50 of 1.8 μM. |
| EZH2-IN-15
EZH2-IN-15 (SHR2554) is a EZH2 inhibitor. |
| NSD-IN-2
NSD-IN-2 is a potent and irreversible NSD1 inhibitor. |
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