Rationally designed multitarget agents against inflammation and pain.
Rationally designed multitarget agents against inflammation and pain.
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DOI：
10.2174/0929867311320130013
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发表时间：
2013
影响因子：
4.1
通讯作者：
Hammock BD
中科院分区：
文献类型：
--
作者：
Hwang SH;Wecksler AT;Wagner K;Hammock BD
花生四烯酸（ARA）经历酶介导的氧化代谢，导致许多生物活性代谢物的形成。一个多世纪以来，这些生化转化一直是众多治疗炎症和疼痛的药物的目标。特别是，非甾体抗炎药（NSAID）和环氧合酶-2（COX-2）选择性抑制剂（昔布）广泛用于治疗炎症和疼痛。然而，非甾体抗炎药和考昔布对胃肠道 (GI) 和心血管的不良影响，以及最近的研究结果表明，当药理学抑制单个 ARA 级联代谢途径时，氧脂质水平的破坏存在显着风险，因此开展了涉及同时抑制 ARA 级联中多个途径的研究。 These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacy or reduce side-effects in the treatment of inflammation and pain.本综述重点关注 ARA 级联的三个途径（环氧合酶 (COX)、脂氧合酶 (LOX) 和细胞色素 P450 (CYP450)）内的串扰，并总结了当前和未来用于治疗类花生酸驱动的炎症和疼痛的多靶点抑制剂的方法。
Arachidonic acid (ARA) undergoes enzyme-mediated oxidative metabolism, resulting in the formation of a number of biologically active metabolites. For over a century, these biochemical transformations have been the target of numerous pharmacological drugs for inflammation and pain. In particular, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs) are widely used in the treatment of inflammation and pain. However, gastrointestinal (GI) and cardiovascular adverse effects of NSAIDs and coxibs, and recent findings demonstrating that there are significant risks from the disruption of oxylipin levels when pharmacologically inhibiting a single ARA cascade metabolic pathway, have led to studies involving the simultaneous inhibition of multiple pathways in ARA cascade. These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacy or reduce side-effects in the treatment of inflammation and pain. This review focuses on the crosstalk within the three pathways of the ARA cascade (cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450)), and summarizes the current and future approaches of multitarget inhibitors for the treatment of eicosanoid driven inflammation and pain.