Development of human 12/15-lipoxygenase therapeutics for stroke

摘要 其目标是开发对中风有效的新疗法。这将通过推进 候选分子的临床应用利用我们的分析级联来鉴定新的， 12/15脂氧合酶选择性抑制剂，可预防缺血性中风。我们的药 发现的方法是合成基于ML351支架的新型配体，这些配体是 人12/15脂氧合酶的有效抑制剂和保护神经元免受氧化的作用 应激相关的细胞死亡。候选分子将接受分析以评估标准 具体涉及治疗环境中化合物的物理化学性质， 包括酶选择性和测试，以确定与关键代谢的潜在相互作用 酶系统。最好的候选人将通过一系列测试进行评估，以防止 小鼠和兔子的实验性中风。

Summary The goal is to develop novel therapeutics effective in stroke. This will be achieved by advancing candidate molecules toward clinical application utilizing our assay cascade to identify novel, selective inhibitors of the 12/15 lipoxygenase that protect against ischemic stroke. Our drug discovery approach will be to synthesize novel ligands based on the ML351 scaffold that are potent inhibitors of the human 12/15 lipoxygenase and that protect neurons against oxidative stress-related cell death. Candidate molecules will undergo profiling to assess criteria specifically related to the physicochemical properties of compounds in a therapeutic setting, including enzyme selectivity and tests to determine potential interactions with key metabolic enzyme systems. Best candidates will be evaluated in a battery of tests for protection against experimental stroke in mice and rabbits.