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LDN-57444 is a novel potent and selective inhibitor of ubiquitin C-terminal hydrolase-L1 (UCH-L1) with IC₅₀ ~0.88 μM. It has ~28-fold greater selectivity over UCH-L3 (ubiquitin C-terminal hydrolase L3).  LDN-57444 can increase levels of highly ubiquitinated proteins and decreases ubiquitin proteasome activity. It causes cell death through the apoptosis pathway. LDN-57444’s activity leads to dramatic alterations in synaptic protein distribution and spine morphology in vivo.

How to Use:

• In vitro:  LDN-57444 was used at 5-25 µM final concentration in various in vitro assays.
• In vivo:  LDN-57444 was administered through IP injection at 0.5 mg/kg in a-syn transgenic mice.

Reference:

• 1. Gong B, et al. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. (2006) Cell. 126(4):775-88.
• 2. Liu Y, et al. Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line. (2003) Chem Biol. 10(9):837-46.
• 3. Tan YY, et al. Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1 inhibitor. (2008) Mol Cell Biochem. 318(1-2):109-15.
• 4. Cartier AE, et al. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1. (2009) J Neurosci. 29(24):7857-68.