338396-68-2Relevant 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.
THE USE OF ARYL PIPERAZINE DERIVATIVES IN MANUFACTURING MEDICANTS FOR TREATING PAIN
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Sheet 5, (2016/08/23)
The use of aryl piperazines of formula (I) in manufacturing a medicament for treating acute pain, neuropathic pain or receptive nociceptive pain in mammals, including human beings is disclosed.
Design, synthesis and biological activity evaluation of arylpiperazine derivatives for the treatment of neuropathic pain
Chen, Yin,Wang, Guan,Xu, Xiangqing,Liu, Bi-Feng,Li, Jianqi,Zhang, Guisen
experimental part, p. 5785 - 5806 (2011/09/20)
In this work, a series of arylpiperazine derivatives were synthesized and screened by in vivo pharmacological trials. Among the tested compounds, 2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)-1-phenylethanone (18) and 2-(4-(2,3-dimethylphenyl)piperazin-
