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.
CAS Number: 668467-91-2
Molecular Weight: 397.64
Chemical Name: (Z)-3-(acetoxyimino)-5-chloro-1-(2,5-dichlorobenzyl)indolin-2-one
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO up to 25 mM
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
LDN-57444 was used at 5-25 µM final concentration in various in vitro assays.
LDN-57444 was administered through IP injection at 0.5 mg/kg in a-syn transgenic mice.
- 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.
- 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.
- 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.
- Cartier AE, et al. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1. (2009) J Neurosci. 29(24):7857-68.
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