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: 10691131
• 负责人: Alexey Zakharov
• 金额: $ 14.62万
• 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/10691131
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Arachidonate 15-Lipoxygenase; Biological Assay; Cells; Collaborations; Development; Disease; Disease model; Goals; In Vitro; Pharmaceutical Chemistry; Proteins; Research; Research Personnel; Role; Structure; Traumatic Brain Injury; Work; analog; base; 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 initiated the collaboration and outlined a research plan to accomplish the stated project goals. Initial work was also done to design and begin development of potential cell-based assays, and a 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/PEBP1蛋白质 - 蛋白质蛋白质复合物并在体外模型中调节铁蛋白的抑制剂来建立先前的筛查工作。在此期间，协作团队启动了合作，并概述了一项研究计划，以实现既定项目目标。还为设计和开始开发潜在的基于细胞的测定法，并讨论了当前15-LOX-2抑制剂铅的药物化学策略。该项目团队已经确定了一个抑制铁吞作用的小分子，目前正在追求化学型的类似物。