Development of human 12/15-lipoxygenase therapeutics for stroke

总结 目标是开发有效治疗中风的新疗法。这将通过推进 利用我们的测定级联来鉴定新的， 12/15脂氧合酶的选择性抑制剂，可预防缺血性中风。我们的毒品 发现方法将是合成基于ML 351支架的新型配体， 人12/15脂氧合酶的有效抑制剂，保护神经元免受氧化损伤 应激相关的细胞死亡候选分子将进行分析，以评估标准 具体涉及化合物在治疗环境中的物理化学性质， 包括酶的选择性和测试，以确定潜在的相互作用与关键代谢 酶系统最佳候选人将在一系列测试中进行评估， 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.