University of Medicine and Pharmacy Grigore T Popa Iasi, Interdisciplinary Medicine , 16 Universitatii Str, Iasi, 700115 , Romania
Expert Opin Ther Targets. 2014 Nov;18(11):1285-92. doi: 10.1517/14728222.2014.945425. Epub 2014 Sep 12.
In asthma and chronic obstructive pulmonary disease (COPD), there is an unmet therapeutic need for the anti-inflammatory therapies, and the identification of therapeutic targets and potent corresponding therapies is necessary. Although inhaled corticosteroids and leukotriene modifiers are most effective in asthma they are still not always capable of appropriately controlling the disease. In COPD, the therapeutic gap is even larger because inhaled corticosteroids and other anti-inflammatory therapies are not beneficial in all disease subsets.
The role of the 5-lipoxygenase-activating protein (FLAP) in generating proinflammatory molecules such as leukotrienes is discussed, highlighting, in particular, its potential as a therapeutic target in asthma and COPD. The preclinical data on FLAP inhibitors are discussed. The clinical data on the FLAP inhibitors investigated so far for these diseases are analyzed.
FLAP inhibitors have emerged during the past decade as a promising therapeutic class in asthma and COPD, but there exists only a limited amount of data supporting their efficacy in these diseases. This might be due to the fact that the development of some of the molecules discussed was abandoned. Such therapies might be of particular interest in COPD and in asthma-COPD overlap syndrome.
在哮喘和慢性阻塞性肺疾病(COPD)中,存在着对抗炎治疗的未满足的治疗需求,因此有必要确定治疗靶点和有效的相应治疗方法。尽管吸入性皮质类固醇和白三烯调节剂在哮喘中最有效,但它们仍不能始终适当地控制疾病。在 COPD 中,治疗差距更大,因为吸入性皮质类固醇和其他抗炎治疗方法并非对所有疾病亚型都有效。
本文讨论了 5-脂氧合酶激活蛋白(FLAP)在生成炎症分子(如白三烯)中的作用,特别强调了其在哮喘和 COPD 中作为治疗靶点的潜力。讨论了 FLAP 抑制剂的临床前数据。分析了迄今为止针对这些疾病研究的 FLAP 抑制剂的临床数据。
FLAP 抑制剂在过去十年中作为哮喘和 COPD 中一种有前途的治疗类别出现,但仅有有限的证据支持它们在这些疾病中的疗效。这可能是由于讨论的一些分子的开发被放弃了。这些疗法可能特别适用于 COPD 和哮喘-COPD 重叠综合征。