Novel 12/15 lipoxygenase inhibitors for the treatment of stroke

描述（由申请人提供）：目标是开发有效治疗中风的新疗法。这将通过将候选分子推向临床应用来实现，利用我们的级联分析来识别新的、选择性的12/15脂氧合酶抑制剂，以防止缺血性中风。我们的药物发现方法将是基于LOXBlock抑制剂合成新的配体，LOXBlock抑制剂是人类12/15脂氧合酶的有效抑制剂，可以保护神经元免受氧化应激相关的细胞死亡。候选分子将进行分析，以评估与治疗环境中化合物的物理化学性质相关的标准，包括酶选择性和确定与关键代谢酶系统潜在相互作用的测试。最佳候选药物将在小鼠身上进行实验性中风保护试验。

DESCRIPTION (provided by applicant): 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 LOXBlock inhibitors 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 tested for protection against experimental stroke in mice.