1793053-37-8

Basic information

• Product Name: LLY-507
• Synonyms: LLY-507;5-Cyano-2'-[4-[2-(3-methyl-1H-indol-1-yl)ethyl]-1-piperazinyl]-N-[3-(1-pyrrolidinyl)propyl]-[1,1'-biphenyl]-3-carboxamide;5-cyano-2'-[4-[2-(3-methyl-1H-indol-1-yl)ethyl]-1-piperazinyl]-N-[3-(1-pyrrol;LLY-507(CHEMBL3414623)
• CAS NO: 1793053-37-8
• Molecular Formula: C36H42N6O
• Molecular Weight: 574.75828
• EINECS: -0
• Mol File: 1793053-37-8.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Solubility: ≥57.5 mg/mL in DMSO; insoluble in H2O; ≥54.7 mg/mL in EtOH
• CAS DataBase Reference: LLY-507(CAS DataBase Reference)
• NIST Chemistry Reference: LLY-507(1793053-37-8)
• EPA Substance Registry System: LLY-507(1793053-37-8)

Safety Data

• Hazardous Substances Data: 1793053-37-8(Hazardous Substances Data)

Usage

Description

LLY-507 is a small molecule inhibitor of SMYD2 (lysine N-methyltransferase), which prevents p53 lysine methylation in squamous cell carcinoma cells. It demonstrates a >100-fold selectivity for SMYD2 over 27 other protein methyltransferases (and non-methyltransferase) targets.

Uses

Used in Pharmaceutical Industry:
LLY-507 is used as a therapeutic agent for the treatment of squamous cell carcinoma. Its ability to inhibit SMYD2 prevents p53 lysine methylation, which plays a crucial role in the development and progression of squamous cell carcinoma.
Used in Cancer Research:
LLY-507 is used as a research tool to study the role of SMYD2 in the regulation of p53 function and its implications in cancer development. Its high selectivity for SMYD2 makes it a valuable compound for investigating the underlying mechanisms of p53 dysregulation in cancer cells.

Biological Activity

lly-507 is a potent inhibitor of smyd2.smyd2, a lysine methyltransferase, catalyzes the monomethylation of several protein substrates including p53. smyd2 is reported to be overexpressed in a significant percentage of esophageal squamous primary carcinomas, and such overexpression related with poor patient survival.

in vitro

lly-507 has been identified as a cell-active, potent small molecule inhibitor of smyd2. lly-507 was found to be >100-fold selective for smyd2 over a broad range of methyltransferase and non-methyltransferase targets. the crystal structure of smyd2 in complex with lly-507 showed it bound in the substrate peptide binding pocket. lly-507 was active in cells as demonstrated by the reduction of smyd2-induced monomethylation of p53 lys(370) at submicromolar concentrations. furthermore, ms-based proteomics indicated that cellular histone methylation levels were not affected by smyd2 inhibition with lly-507 significantly, and subcellular fractionation studies showed that smyd2 was primarily cytoplasmic, indicating that smyd2 targeted a small subset of histones. moreover, lly-507 was able to inhibit the proliferation of several liver, esophageal, as well as breast cancer cell lines in a dose-dependent manner [1].

IC 50

< 15 nm

references

[1] nguyen h, et al. lly-507, a cell-active, potent, and selective inhibitor of protein-lysine methyltransferase smyd2. j biol chem. 2015 may 29;290(22):13641-13653.