LDN-57444

SKU: orb1224289

Description

A reversible, competitive, active site-directed Uch-L1 inhibitor with IC50 of 0.88 uM; shows weak inhibition on Uch-L3 (IC50> 20 uM); causes cell death through the apoptosis pathway by decreasing the activity of ubiquitin proteasome system and increasing the levels of highly ubiquitinated proteins, both of which can activate UPR.

Key Properties

• CAS Number: 668467-91-2
• MW: 397.6398
• Purity: >98% (HPLC)
• Formula: C₁₇H₁₁Cl₃N₂O₃
• SMILES: O=C1N(CC2=CC(Cl)=CC=C2Cl)C3=C(C=C(Cl)C=C3)/C1=N/OC(C)=O
• Target: DUB
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  LDN-57444 (0.4 mg/kg, i.p.) blocks the beneficial effect of V-Uch-L1, and worsens contextual conditioning performance as the mice are exposed to the context at 1, 7, 14, and 21 days after training.
• In Vitro:
  LDN-57444 is a reversible, competitive inhibitor of UCH-L1, with an IC50 of 0.88 μM, and also suppresses UCH-L3 activity, with an IC50 of 25 μM. LDN-57444 (LDN, 5 μM for 1 hr) inhibits 70% of Uch activity in hippocampal slices of the mouse brain. LDN-57444 (5 μM for 2 hr) does not reduce potentiation further in APP/PS1 slices or in wt slices exposed to 200 nM Aβ. LDN-57444 (25-100 μM) inhibits ubiquitin-proteasome activity dose-dependently in SK-N-SH cells. LDN-57444 (50 μM) also induces apoptotic cell death, causes the endoplasmic reticulum stress and results in expression of spliced XBP-1(XBP-1s, 48KD) in SK-N-SH cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ubiquitin C-terminal Hydrolase L1 Inhibitor | UCH-L1 Inhibitor

Quick Database Links

Gene Symbol

DUB