University of Athens, Department of Chemistry, Panepistimiopolis, Athens 15771, Greece.
Expert Opin Ther Pat. 2010 Jan;20(1):1-18. doi: 10.1517/13543770903463905.
The various phospholipase A(2) (PLA(2)) types have been implicated in diverse kinds of lipid signaling and inflammatory diseases. Rheumatoid arthritis, lung inflammation, neurological disorders, such as multiple sclerosis, cardiovascular diseases, including atherosclerosis, and cancer are included among the diseases where PLA(2) enzymes are involved. Thus, there is a great interest in developing potent and selective PLA(2) inhibitors and some of them have entered clinical trials.
This review article discusses the role of each PLA(2) class in inflammatory diseases and the advances in the development of inhibitors presented in patent literature from January 2004 to May 2009.
PLA(2)s cluster in four main types: secreted sPLA(2), cytosolic cPLA(2), Ca(2+)-independent iPLA(2) and lipoprotein-associated LpPLA(2). Each of those types has been implicated in diverse kinds of inflammatory diseases. Readers will rapidly gain an overview of the various PLA(2) inhibitors reported in the patent literature in the past 5 years. Furthermore, the readers will learn the difficulties related to the development of PLA(2) inhibitors as new drugs and also the different companies and research groups that are the main players in the field.
Although the role of each PLA(2) is not yet distinct in different diseases, the development and future use of different PLA(2) inhibitors to treat human disease seems very promising.
各种磷脂酶 A(2)（PLA(2)）已被牵连到各种脂质信号和炎症性疾病中。类风湿关节炎、肺部炎症、神经紊乱，如多发性硬化症、心血管疾病，包括动脉粥样硬化、和癌症都包括在涉及 PLA(2)酶的疾病中。因此，人们对开发有效的、选择性的 PLA(2)抑制剂有很大的兴趣，其中一些已经进入临床试验。
这篇综述文章讨论了每种 PLA(2)类在炎症性疾病中的作用，以及 2004 年 1 月至 2009 年 5 月专利文献中报道的抑制剂的进展。
PLA(2)分为四大类：分泌型 sPLA(2)、胞浆型 cPLA(2)、Ca(2+)非依赖性 iPLA(2)和脂蛋白相关 LpPLA(2)。这些类型都与各种炎症性疾病有关。读者将快速了解过去 5 年专利文献中报道的各种 PLA(2)抑制剂。此外，读者将了解到开发 PLA(2)抑制剂作为新药所面临的困难，以及在该领域中处于主要地位的不同公司和研究小组。
尽管每种 PLA(2)在不同疾病中的作用尚不清楚，但开发和未来使用不同的 PLA(2)抑制剂来治疗人类疾病似乎非常有希望。
