60656-53-3Relevant academic research and scientific papers
Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson's Disease Treatment
Ouyang, Liang,Zhang, Lan,Zhang, Shouyue,Yao, Dahong,Zhao, Yuqian,Wang, Guan,Fu, Leilei,Lei, Peng,Liu, Bo
supporting information, p. 2776 - 2792 (2018/04/23)
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). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SY5Y cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SY5Y cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.
Target autophagy agonist and application thereof in neurodegenerative disease treating medicine
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Paragraph 0064; 0065; 0066; 0067, (2017/07/20)
The invention relates to a target autophagy agonist and application thereof in a neurodegenerative disease treating medicine and belongs to the technical field of neurodegenerative disease resisting pharmacy. The invention aims at providing a compound serving as ULK1 agonist. The compound is prepared from following shown compound or pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof can serve as the ULK1 agonist and has certain neurodegenerative disease resisting activity.
An 'easy-on, easy-off' protecting group for the enzymatic resolution of (±)-1-phenylethylamine in an aqueous medium
Guranda, Dorel T.,Khimiuk, Andrey I.,Van Langen, Luuk M.,Van Rantwijk, Fred,Sheldon, Roger A.,Svedas, Vytas K.
, p. 2901 - 2906 (2007/10/03)
A new approach has been developed for the biocatalytic resolution of (±)-1-phenylethylamine in 100% aqueous medium based on two integrated enzymatic steps: protection and deprotection of the reactive amine enantiomer catalyzed by the same enzyme-penicillin acylase from Alcaligenes faecalis. An 'easy-on, easy-off' protecting group has been introduced using (R)-phenylglycine amide as the acyl donor. (R)-Phenylglycyl-substituted (R)-1-phenylethylamine was poorly soluble and precipitated at enzymatic acylation in an alkaline medium (pH 10-11), driving the synthesis towards high yields. Conversely at pH 7.5, its solubility was continuously increasing, which rendered the subsequent deacylation by the same enzyme highly efficient. In contrast to the resolutions, which employ one biocatalytic step, the new approach made it possible to exploit two sequential enantioselective enzymatic reactions implementing a double enantioselectivity control. Effective enzymatic resolution of (±)-1-phenylethylamine in an aqueous medium was performed with (R)-phenylglycine amide as an acyl donor using the suggested approach.
