LDN-57444

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 μM⁴. 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 μM⁵. 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 PSD95⁴.

溶解方案(细胞实验)

DMSO 中的溶解度 : 25 mg/mL (62.87 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (6.29 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"

"方案 一": "请依序添加每种溶剂：50% PEG300 50% SalineSolubility: 10 mg/mL (25.15 mM); 悬浊液; 超声助溶"