| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
LLY-507 targets SMYD2 (SET and MYND domain-containing protein 2), a protein lysine methyltransferase. SMYD2 catalyzes the methylation of histone H3 at lysine 36 (H3K36) and also methylates non-histone proteins such as p53 (at lysine 370), thereby regulating their function. By inhibiting SMYD2, LLY-507 reduces H3K36 methylation and p53 methylation, affecting gene expression and cell cycle regulation. SMYD2 is implicated in cancer, and its inhibition represents a potential therapeutic strategy.
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| 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].
In vitro, LLY-507 inhibits SMYD2 with an IC50 of approximately 15 nM. It shows high selectivity for SMYD2 over other histone methyltransferases and protein lysine methyltransferases. In cellular assays, LLY-507 reduces H3K36me2 levels and p53K370me1 levels in a dose-dependent manner. It also inhibits the proliferation of cancer cells that depend on SMYD2 activity. Detailed cellular IC50 values for growth inhibition are not extensively reported. |
| ln Vivo |
In vivo, LLY-507 has shown antitumor activity in preclinical models. It reduces tumor growth in xenograft models of cancers with SMYD2 overexpression. The compound is orally bioavailable and has been used in animal studies to demonstrate target engagement (reduction of H3K36me2 and p53K370me1 in tumors). Detailed in vivo efficacy data are not extensively reported in the available literature.
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| Enzyme Assay |
Non-cell-based enzyme assays for LLY-507 use purified SMYD2 enzyme. The compound is incubated with the enzyme, a peptide substrate (e.g., histone H3 peptide), and the methyl donor S-adenosylmethionine (SAM) at varying concentrations. Methyltransferase activity is measured by quantifying the transfer of methyl groups to the substrate using radiometric (3H-SAM), fluorescence-based, or mass spectrometry methods. IC50 values for enzyme inhibition are determined from dose-response curves. Selectivity profiling against other methyltransferases is performed to confirm specificity.
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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. Cellular assays for LLY-507 utilize cancer cell lines with SMYD2 expression. Cells are treated with the compound at various concentrations for specified durations. H3K36me2 and p53K370me1 levels are measured by Western blotting using specific antibodies. Cell proliferation is assessed using standard viability assays (e.g., MTT, CellTiter-Glo). Cell cycle analysis and apoptosis assays are performed to assess the functional consequences of SMYD2 inhibition. Target gene expression changes are measured by RNA-seq or qPCR. |
| Animal Protocol |
In vivo animal models for LLY-507 include xenograft studies in immunodeficient mice bearing cancer cell lines with SMYD2 overexpression. The compound is administered orally at various doses. Tumor growth is monitored by caliper measurements. Tumor tissues are collected for analysis of H3K36me2 and p53K370me1 levels to confirm target engagement. Toxicity is monitored by body weight and organ histology. Detailed protocols are not extensively reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of LLY-507 include CAS number 1793053-37-8. The compound is a small molecule SMYD2 inhibitor. It is orally bioavailable. Detailed PK parameters such as molecular weight, half-life, and bioavailability are not extensively reported in the available literature. The compound is supplied as a research reagent for laboratory use only.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for LLY-507 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only. Given its mechanism of SMYD2 inhibition, potential effects on epigenetic regulation in normal tissues would be key safety considerations.
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| References | |
| Additional Infomation |
LLY-507 is a secondary amide formed by the condensation of the carboxyl 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-(pyrrolidone-1-yl)propyl-1-amine. It is a potent and selective SMYD2 inhibitor that inhibits the methylation of p53 by SMYD2. LLY-507 can serve as an important chemical probe for elucidating the function of SMYD2 in cancer and other biological processes. It also acts as an EC 2.1.1.354 (histone H3-lysine(4) N-trimethyltransferase) inhibitor. It is a methylindole, N-alkylpiperazine, N-arylpiperazine, nitrile, benzamide, secondary carboxamide, and N-alkylpyrrolidine compound.
LLY-507 is a potent and selective inhibitor of SMYD2. It has CAS number 1793053-37-8. It has an IC50 of approximately 15 nM for SMYD2 and shows high selectivity over other methyltransferases. It reduces H3K36me2 and p53K370me1 levels in cells. It has shown antitumor activity in preclinical models. It is used as a research tool for studying SMYD2 biology and epigenetic regulation in cancer. It is for research use only. |
| 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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| SMILES |
CC1=CN(C2=CC=CC=C12)CCN3CCN(CC3)C4=CC=CC=C4C5=CC(=CC(=C5)C#N)C(=O)NCCCN6CCCC6
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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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