Improving 15-LOX-2 small molecule inhibitors through medicinal chemistry and structure-guided design

通过药物化学和结构引导设计改进 15-LOX-2 小分子抑制剂

• 批准号: 10919696
• 负责人: Alexey Zakharov
• 金额: $ 12.58万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10919696
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Arachidonate 15-Lipoxygenase; Biological Assay; Cells; Disease; Disease model; Goals; In Vitro; Pharmaceutical Chemistry; Proteins; Research; Research Personnel; Role; Structure; Traumatic Brain Injury; Work; analog; design; improved; in vivo Model; inhibitor; protein complex; screening; small molecule; small molecule inhibitor

This project aims to build on previous screening work by developing selective and potent 15-LOX-2 inhibitors, specifically ones capable of disrupting the 15-LOX-2/PEBP1 protein-protein complex and modulate ferroptosis both in in vitro and in vivo models. During this period, the collaborative team worked to outline a research plan to accomplish the stated project goals. Initial work was done to design and develop potential cell-based assays, and medicinal chemistry strategies were discussed for the current 15-LOX-2 inhibitor leads. The project team has identified a small molecule that inhibits ferroptosis, and is currently pursuing analogs of the chemotype.

该项目旨在通过开发选择性和有效的15-LOX-2抑制剂，特别是能够破坏15-LOX-2/PEBP 1蛋白质-蛋白质复合物并在体外和体内模型中调节铁凋亡的抑制剂，来建立以前的筛选工作。 在此期间，合作团队致力于概述一项研究计划，以实现既定的项目目标。最初的工作是设计和开发潜在的基于细胞的测定，并讨论了目前15-LOX-2抑制剂的药物化学策略。该项目小组已经确定了一种抑制铁凋亡的小分子，目前正在寻找化学型的类似物。