SBIR Phase I: Structure-guided design of anti-inflammatory modulators of protease-activated receptor 1 (PAR1)

SBIR I 期：蛋白酶激活受体 1 (PAR1) 抗炎调节剂的结构引导设计

• 批准号: 2223225
• 负责人: Christopher Dockendorff
• 金额: $ 27.47万
• 依托单位: FUNCTION THERAPEUTICS, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2223225&HistoricalAwards=false
• 关键词: SBIR; Phase; Structure; guided; design

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is that a deeper structural understanding will be developed of protease-activated receptor 1 (PAR1), an important target for promising new anti-thrombotic and anti-inflammatory drugs. The project will also support the development of new compounds targeting PAR1 with the potential for improved potency and safety profiles. Such compounds could represent a new drug class for the treatment of inflammation-related diseases, including kidney disease.The proposed project involves the confirmation of the binding site on PAR1 of small molecule ligands called parmodulins. A detailed characterization of this binding site will support the rapid design, synthesis, and testing of new and improved parmodulins with superior properties as oral medications. A combination of computational, structural biology, and synthetic methods will be combined with PAR1 cell assays to confirm the binding site and develop more detailed structure-activity relationships of the parmodulins. It is also anticipated that novel parmodulins will be identified in this project with improved safety and stability profiles.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）I阶段项目的更广泛影响是，将对蛋白酶激活的受体1（PAR1）产生更深入的结构理解，这是有望提供新的抗血清和抗炎药的重要目标。该项目还将支持针对PAR1的新化合物的开发，并有可能提高效力和安全性。这种化合物可以代表一种新药物，用于治疗炎症相关疾病，包括肾脏疾病。拟议的项目涉及在称为parmodulins的小分子配体PAR1上确认结合位点。该结合位点的详细表征将支持具有出色特性作为口服药物的新的和改进的偏多素的快速设计，合成和测试。计算，结构生物学和合成方法的结合将与PAR1细胞测定法相结合，以确认结合位点并发展出parmodulins的更详细的结构活性关系。还可以预料，在该项目中将确定新型的parmodulins具有改进的安全性和稳定性配置文件。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的审查标准，被认为值得通过评估来获得支持。