[Controlling arachidonic acid metabolic network: from single- to multi-target inhibitors of key enzymes].
Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.
Liu
Ying
Y
College of Chemistry and Molecular Engineering, BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Peking University, Beijing 100871, China. liuying@pku.edu.cn
Chen
Zheng
Z
Shang
Er-chang
EC
Yang
Kun
K
Wei
Deng-guo
DG
Zhou
Lu
L
Jiang
Xiao-lu
XL
He
Chong
C
Lai
Lu-hua
LH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016859:Lipoxygenase Inhibitors; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D064801:Phospholipase A2 Inhibitors; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D054467:Phospholipases A2; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase