LDN-57444

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种可逆、竞争性、活性定点 Uch-L1 抑制剂，IC50 为 0.88 uM。

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.

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.

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.

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

Proteasome/Ubiquitin

DUB

UCH-L1|UCH-L3

Neurological Disease

——

668467-91-2

397.6398

C17H11Cl3N2O3

>98% (HPLC)

10 mM in DMSO

O=C1N(CC2=CC(Cl)=CC=C2Cl)C3=C(C=C(Cl)C=C3)/C1=N/OC(C)=O

1H-Indole-2,3-dione, 5-chloro-1-[(2,5-dichlorophenyl)methyl]-, 3-(O-acetyloxime)

(-20℃)

With Ice Pack

≥ 2 years