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LDN-57444

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Chemical Structure| 668467-91-2 同义名 : Ubiquitin C-terminal Hydrolase L1 Inhibitor;UCH-L1 Inhibitor
CAS号 : 668467-91-2
货号 : A388744
分子式 : C17H11Cl3N2O3
纯度 : 99%+
分子量 : 397.64
MDL号 : MFCD09037562
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(62.87 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+corn oil 6 mg/mL

生物活性
靶点

  • UCH

    UCH-L1, IC50:0.4 μM

    UCH-L3, IC50:25 μM
描述 Deubiquitinating enzymes (DUBs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. The DUB ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a component of the ubiquitin proteasome system (UPS), it is abundantly expressed in neuronal brain cells and has been connected to Parkinson’s disease (PD)[3]. LDN-57444 is a specific inhibitor of UCH-L1 with IC50 value of 0.88 μM[4]. In vitro, LDH-57444 treatment significantly inhibited proteasome activity in a concentration-dependent manner at 25 μM and above, and treatment with 50 μM LDH-5744 for 24h led to 70% inhibition of the proteasome activity in human neuroblastoma SK-N-SH cells. LDN-57444 greatly reduced the cell viability and induced apoptosis of SK-N-SH cells at concentration ranging in 25 – 100 μM[5]. In vivo, LDN-57444 had an inhibitory effect on UCHL1 in the hippocampus at systemic doses of 0.5 mg/kg. Administration LDN-57444 at dose of 1 mg/kg for 4h significantly inhibited levels of free monomeric ubiquitin in mice. However, high dose LDN-57444 (2.5 mg/kg) increased UCHL1 expression, possibly as a compensatory mechanism. In addition, both 1 mg/kg and 2.5 mg/kg doses of LDN57444 depleted the hippocampus of postsynaptic density protein PSD95[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.51mL

0.50mL

0.25mL

12.57mL

2.51mL

1.26mL

25.15mL

5.03mL

2.51mL
参考文献

[1]Cartier AE, Ubhi K, et al. Differential effects of UCHL1 modulation on alpha-synuclein in PD-like models of alpha-synucleinopathy. PLoS One. 2012;7(4):e34713.

[2]Liu Y, Lashuel HA, et al. Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line. Chem Biol. 2003 Sep;10(9):837-46.

[3]Pukaß K, Richter-Landsberg C. Inhibition of UCH-L1 in oligodendroglial cells results in microtubule stabilization and prevents α-synuclein aggregate formation by activating the autophagic pathway: implications for multiple system atrophy. Front Cell Neurosci. 2015 May 5;9:163.

[4]Reynolds JP, Jimenez-Mateos EM, Cao L, Bian F, Alves M, Miller-Delaney SF, Zhou A, Henshall DC. Proteomic Analysis After Status Epilepticus Identifies UCHL1 as Protective Against Hippocampal Injury. Neurochem Res. 2017 Jul;42(7):2033-2054.

[5]Tan YY, Zhou HY, Wang ZQ, Chen SD. Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1 inhibitor. Mol Cell Biochem. 2008 Nov;318(1-2):109-15.