LDN 57444
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.
| Physical Appearance | A solid |
| Storage | Desiccate at 4°C |
| M.Wt | 397.64 |
| Cas No. | 668467-91-2 |
| Formula | C17H11Cl3N2O3 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥16.7 mg/mL in DMSO with gentle warming |
| Chemical Name | [(Z)-[5-chloro-1-[(2,5-dichlorophenyl)methyl]-2-oxoindol-3-ylidene]amino] acetate |
| SDF | Download SDF |
| Canonical SMILES | CC(=O)ON=C1C2=C(C=CC(=C2)Cl)N(C1=O)CC3=C(C=CC(=C3)Cl)Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1,2]: | |
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Cell lines |
Rat insulinoma cell line INS 832/13, SK-N-SH cells |
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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. |
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Reacting condition |
30 μM, 24 h |
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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 experiment [1]: | |
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Animal models |
APP/PS1 Mice |
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Dosage form |
Intraperitoneal injection, 0.4 mg/kg |
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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. |
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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. |
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References: [1]. Gong B, Cao Z, Zheng P, et al. Ubiquitin hydrolase Uch-L1 rescues β-amyloid-induced decreases in synaptic function and contextual memory[J]. Cell, 2006, 126(4): 775-788. [2]. Tan Y Y, Zhou H Y, Wang Z Q, et al. Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1 inhibitor[J]. Molecular and cellular biochemistry, 2008, 318(1-2): 109-115. | |
| Description | LDN 57444 is an inhibitor of ubiquitin C-terminal hydrolase-L1 (UCH-L1) with Ki value of 0.4 μM. | |||||
| Targets | UCH-L1 | |||||
| IC50 | 0.4 μM (Ki) | |||||
Quality Control & MSDS
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Chemical structure
