Recent Advances in the Search for Novel 5‐Lipoxygenase Inhibitors (original) (raw)

“…Clinically relevant LT-modifying agents include inhibitors of FLAP or 5-LO, which are currently under clinical investigation as candidates for the treatment of respiratory and cardiovascular diseases (18,19). Despite intensive research, only the direct 5-LO inhibitor zileuton entered the market as an antiasthmatic drug, while other compounds failed in clinical trials due to lack of efficacy Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP).…”

Section: Introductionmentioning

“…), in female mice (Table 2). Taking or toxicity (19). However, either published studies did not examine sex subgroups separately or sex-related effects were not reported.…”

Section: Introductionmentioning

“…With this goal in mind, we chronically administered zileuton, an orally available and irreversible 5LO activation inhibitor (Steinhilber & Hofmann, 2014), to the P301S mice starting at 3 months of age. After 7 months of treatment, we found that P301S mice receiving zileuton when compared with P301S receiving vehicle displayed a significant improvement in their memory as shown in the Y‐maze paradigm, which by recording spontaneous alternation behavior assesses short‐term and working memory.…”

Section: Discussionmentioning

“…The 5-LO-derived arachidonic acid metabolites have been shown to be potent mediators of inflammatory reactions [4]. During the last decades, many investigations demonstrated that the 5-LO pathway plays a role in the development of allergic diseases such as asthma and inflammatory disorders.…”

Section: Introductionmentioning

“…Moreover, there is some evidence that the 5-LO pathway could be involved in tumorigenesis, especially in prostate cancer and certain forms of leukaemia. Up to now, only one 5-LO inhibitor is on the market, zileuton for the treatment of asthma [4].…”

Section: Introductionmentioning