668467-91-2

Basic information

• Product Name: LDN-57444
• Synonyms: LDN-57444;5-Chloro-1-[(2,5-dichlorophenyl)methyl]-1H-indole-2,3-dione3-(O-acetyloxime);LDN-57444/LDN57444;1H-Indole-2,3-dione, 5-chloro-1-[(2,5-dichlorophenyl)methyl]-, 3-(O-acetyloxime);5-Chloro-1-[(2,5-dichlorophenyl)methyl]-1H-indole-2,3-dione 3-(O-acetyloxime) LDN 57444;3-(O-acetyloxime), 5-chloro-1-[(2,5-dichlorophenyl)methyl]-1H-Indole-2,3-dione;LDN 57444, >=98%;UCH-L1 Inhibitor
• CAS NO: 668467-91-2
• Molecular Formula: C17H11Cl3N2O3
• Molecular Weight: 397.63984
• Product Categories: Inhibitors
• Mol File: 668467-91-2.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 534.4±60.0 °C(Predicted)
• Appearance: /
• Density: 1.50±0.1 g/cm3(Predicted)
• Storage Temp.: Desiccate at +4°C
• Solubility: DMSO: soluble16mg/mL
• PKA: -2.57±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 week.
• CAS DataBase Reference: LDN-57444(CAS DataBase Reference)
• NIST Chemistry Reference: LDN-57444(668467-91-2)
• EPA Substance Registry System: LDN-57444(668467-91-2)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 668467-91-2(Hazardous Substances Data)

Usage

Description

LDN-57444 is a potent and selective inhibitor of ubiquitin C-terminal hydrolase L1 (UCH-L1), a de-ubiquitinating enzyme involved in various cellular processes, including protein degradation and synaptic function. It has an IC50 of 0.88 μM and a Ki of 0.4 μM, demonstrating its high affinity and selectivity for UCH-L1 over other UCH enzymes, such as UCH-L3. The inhibition of UCH-L1 by LDN-57444 leads to cell death through the apoptosis pathway due to impaired ubiquitin-proteasome function, making it a potential therapeutic agent for various diseases.

Uses

Used in Pharmaceutical Industry:
LDN-57444 is used as an inhibitor of UCH-L1 for its potential therapeutic applications in treating diseases associated with the enzyme's dysregulation. Its ability to induce cell death through apoptosis makes it a promising candidate for the development of drugs targeting cancer and neurodegenerative disorders, such as Parkinson's disease and neuropathic pain.
Used in Cancer Research:
LDN-57444 is used as a research tool to study the role of UCH-L1 in tumor progression and the ubiquitin-proteasome pathway. Its selectivity for UCH-L1 allows researchers to investigate the enzyme's function in lung tumor-derived cell lines and other cancer types, providing insights into potential therapeutic targets and strategies for cancer treatment.
Used in Neurodegenerative Disease Research:
LDN-57444 is used as a research tool to explore the involvement of UCH-L1 in neurodegenerative diseases, such as Parkinson's disease. Its ability to induce cell death through the apoptosis pathway and alter synaptic structure and function makes it a valuable compound for studying the underlying mechanisms of these diseases and identifying potential therapeutic interventions.
Used in Drug Development:
LDN-57444 is used as a lead compound in the development of new drugs targeting UCH-L1 for the treatment of various diseases. Its high affinity and selectivity for the enzyme, as well as its ability to induce cell death through apoptosis, make it a promising starting point for the design and optimization of novel therapeutic agents.

References

1) Liu et al. (2003), Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line; Chem. Biol., 10 837 2) Tan et al. (2008), Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1 inhibitor; Mol. Cell. Biochem., 318 109 3) Cartier et al. (2009), Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1; J. Neurosci., 29 7857

Biochem/physiol Actions

LDN-57444 is a potent, reversible, competitive and active site-directed inhibitor of UCHL1