siRNA Library Screening for Pharmacologic Radiation Mitigators

药物放射缓解剂的 siRNA 文库筛选

• 批准号: 8718985
• 负责人: JOHN S. LAZO
• 金额: $ 27.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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/8718985
• 关键词: Adopted; Animal Model; Apoptosis; BCL2 gene; Biological Assay; Biological Markers; Cardiolipins; Cell Culture Techniques; Cells; Collaborations; Complex; Computer Analysis; Computing Methodologies; Development; Drug Kinetics; Drug Targeting; Drug usage; Ensure; Exposure to; General Population; Genome; Glyburide; Human; Lead; Link; Mitochondria; Molecular Target; New Agents; Nitric Oxide Synthase; Nuclear; Oleic Acids; Oxidoreductase; Pathway interactions; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Proteins; RNA; RNA Interference; RNA library; Radiation; Radiation Toxicity; Radioactive; Resources; Sentinel; Stabilizing Agents; Standardization; Structure; System; Tissues; Toxic effect; War; analog; combat; design; drug discovery; inhibitor/antagonist; innovation; irradiation; nanoparticle; nitration; novel; programs; screening; small molecule; small molecule libraries

Ionizing irradiation induces RNAs in cells which can be targeted prior to irradiation by siRNA to identify novel targets for radioprotector drugs. We have successfully used this strategy to identify a co,mmon drug, Glyburide, as a novel radioprotector. We now propose to apply this strategy to identify radiation mitigator drugs using radiosensitive human cell targets and siRNA screening after irradiation. The 1** Specific Aim will optimize and deploy sentinel cells for detecting RNA targets for new mitigator drugs. The second aim will be to use druggable siRNA libraries and small molecule libraries to identify radiation damage mitigators. The third aim will be to identify targets that interact positively with prioritized drugs to advance radiation mitigation effects.

电离辐射会在细胞中诱导 RNA，这些 RNA 可以在辐射之前通过 siRNA 进行靶向，从而识别新的 RNA 放射防护药物的靶标。我们已经成功地使用这种策略来识别一种常见药物， 格列本脲，作为一种新型辐射防护剂。我们现在建议应用这一策略来识别辐射缓解剂 使用放射敏感的人体细胞靶标和辐射后的 siRNA 筛选药物。 1** 具体目标将 优化和部署前哨细胞来检测新缓解药物的 RNA 靶标。第二个目标将是 使用可药物化 siRNA 文库和小分子文库来鉴定辐射损伤缓解剂。这 第三个目标是确定与优先药物积极相互作用的目标，以促进辐射缓解 影响。