自交轴蛋白
溶血磷脂酸
溶血磷脂酰胆碱
磷酸二酯酶
癌症研究
信号转导
受体
医学
化学
药理学
生物
生物化学
细胞生物学
酶
磷脂
膜
磷脂酰胆碱
作者
Yi Jia,Yan Li,Xudong Xu,Yu Tian,Hai Shang
出处
期刊:Pharmaceuticals
[MDPI AG]
日期:2021-11-22
卷期号:14 (11): 1203-1203
被引量:17
摘要
Autotaxin (ATX) is the only enzyme of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP2) family with lysophospholipase D (lysoPLD) activity, which is mainly responsible for the hydrolysis of extracellular lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA can induce various responses, such as cell proliferation, migration, and cytokine production, through six G protein-coupled receptors (LPA1-6). This signaling pathway is associated with metabolic and inflammatory disorder, and inhibiting this pathway has a positive effect on the treatment of related diseases, while ATX, as an important role in the production of LPA, has been shown to be associated with the occurrence and metastasis of tumors, fibrosis and cardiovascular diseases. From mimics of ATX natural lipid substrates to the rational design of small molecule inhibitors, ATX inhibitors have made rapid progress in structural diversity and design over the past 20 years, and three drugs, GLPG1690, BBT-877, and BLD-0409, have entered clinical trials. In this paper, we will review the structure of ATX inhibitors from the perspective of the transformation of design ideas, discuss the advantages and disadvantages of each inhibitor type, and put forward prospects for the development of ATX inhibitors in the future.
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