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BL-918

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Chemical Structure| 2101517-69-3 同义名 : -
CAS号 : 2101517-69-3
货号 : A1250770
分子式 : C23H15F8N3OS
纯度 : 99%+
分子量 : 533.437
MDL号 : MFCD31693829
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: 250 mg/mL(468.66 mM)，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：
生物活性
描述 UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). BL-918 is a novel ULK1 activator that potently activates ULK1 with an EC50 of 24.14 nM. BL-918 could enhance the phosphorylation level of mAtg13 in HEK-293T cells transfected with ULK1WT, indicating BL-918 activates ULK1 in vitro. BL-918 (5 μM; 24 h) treatment induced some vacuolar elements that were most likely to be of autophagic origin in SH-SY5Y cells. BL-918 (5 μM for 0, 6, 12, 24, and 36 h) time-dependently elevated the expression levels of LC3-II (a key marker of autophagy), Beclin-1, and its phosphorylation status, whereas the level of the selective autophagy substrate SQSTM1/p62 was reduced after treatment with BL-918. Moreover, LC3 and SQSTM1/p62 were significantly accumulated after 24 h cotreatment with BL-918 (5 μM) and Bafilomycin A1 (10 nM), indicating that BL-918 treatment enhances the autophagic flux. Interestingly, BL-918 (5 μM; 24 h) treatment induced autophagosome accumulation in PC-12 cells, which was indicated by increased expression levels of LC3-II and SQSTM1/p62, as well as the aggregated LC3 puncta in PC-12 cells. Meanwhile, BL-918 (5 μM; 24 h) treatment led to the increase of the GFP-LC3 puncta in SH-SY5Y cells, which was markedly decreased under the treatment of 3-MA (2 mM; 24 h; a class III PI3K autophagy inhibitor, could block BL-918-induced autophagy). MPP+ (1 mM) was added to SH-SY5Y cells with 0.5, 5, and 50 μM BL-918 with or without 2 mM 3-MA. BL-918 could partially reverse MPP+-induced cell death, which was determined by enhancing cell viability. In a MPTP-induced PD mouse model, the time to turn and time to finish for the MPTP-treated mice were longer than that for the vehicle-treated mice, which are significantly restored in the median- (40 mg/kg) and high-dose (80 mg/kg) BL-918-treated mice demonstrating that BL-918 has a good therapeutic potential on PD models in vivo[1].
作用机制 Some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and BL-918 by site-directed mutagenesis[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.87mL

0.37mL

0.19mL

9.37mL

1.87mL

0.94mL

18.75mL

3.75mL

1.87mL
参考文献

[1]Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson's Disease Treatment