Institute of Pharmaceutical Chemistry, OSF/ZAFES/TMP, Goethe-University of Frankfurt, Frankfurt, Germany.
Basic Clin Pharmacol Toxicol. 2014 Jan;114(1):83-91. doi: 10.1111/bcpt.12134. Epub 2013 Oct 11.
Modulators of the arachidonic acid cascade have been in the focus of research for treatments of inflammation and pain for several decades. Targeting this complex pathway experiences a paradigm change towards the design and development of multi-target inhibitors, exhibiting improved efficacy and less undesired side effects. This minireview summarizes recent developments in the field of designed multi-target ligands of the arachidonic acid cascade. In addition to the well-known dual inhibitors of 5-lipoxygenase and cyclooxygenase-2 such as licofelone, very recent developments are discussed. Especially, multi-target inhibitors interfering with the cytochrome P450 pathway via inhibition of soluble epoxide hydrolase seem to offer a novel opportunity for development of novel anti-inflammatory drugs.
几十年来，花生四烯酸级联的调节剂一直是治疗炎症和疼痛的研究重点。针对这一复杂途径的研究正在朝着设计和开发多靶点抑制剂的方向发生范式转变，这些抑制剂具有更好的疗效和更少的不良反应。这篇综述总结了花生四烯酸级联设计的多靶点配体领域的最新进展。除了众所周知的 5-脂氧合酶和环氧化酶-2 的双重抑制剂，如 licofelone，还讨论了最近的进展。特别是，通过抑制可溶性环氧化物水解酶来干扰细胞色素 P450 途径的多靶点抑制剂似乎为开发新型抗炎药物提供了新的机会。
