Cell lines

Rat insulinoma cell line INS 832/13, SK-N-SH cells

Preparation method

The solubility of this compound in DMSO is >16.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

30 μM, 24 h

Applications

In rat insulinoma cell line INS 832/13, LDN 57444 induced cell apoptosis. LDN 57444 (>30 μM) increased the activity of caspase-3. LDN 57444 induced nuclear CHOP, suggesting that the apoptosis induced by the inhibition of Uch-L1. In SK-N-SH cells, LDN 57444 (25-100 μM) induced apoptotic cell death in SK-N-SH cells. LDN 57444 triggered the endoplasmic reticulum stress in SK-N-SH cells.

Animal models

APP/PS1 Mice

Dosage form

Intraperitoneal injection, 0.4 mg/kg

Application

LDN 57444 caused dramatic alterations in synaptic protein distribution and spine morphology in vivo. Treatment with LDN 57444 resulted in a rapid fall of Uch-L1 activity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

LDN 57444 is a reversible competitive inhibitor of ubiquitin C-terminal hydrolase L1 (Uch-L1) with IC50 value of 0.88μM [1].

Besides Uch-L1, LDN 57444 also inhibits Uch-L3 with a higher IC50 value of 25μM. The inhibition of Uch enzymes subsequently causes the reduction of long-term potentiation and basal synaptic transmission, which is similar to the alterations induced by Aβ [1].

In rat insulinoma cell line INS 832/13, treatment of LDN 57444 leads to the cell apoptosis. The increased activity of caspase-3 can be seen when the concentration of LDN 57444 is above 30μM. LDN 57444 also induces nuclear CHOP, suggesting that the apoptosis induced by the inhibition of Uch-L1 is related to ER stress [2].

References:
[1] Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88.
[2] Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88.