I-Corps: Translation Potential of a High Throughput Drug Discovery Platform for Protein Degraders

这个I-Corps项目的重点是开发一个药物发现平台，以有效地产生一类新的药物。该技术有助于生成广泛的药物库，使可观察特征的无偏筛选成为可能。重要的是，这种方法消除了对蛋白质靶点或特定化学物质的先验知识的需要。利用这个平台，研究人员可以探索潜在药物的广阔前景，并灵活地专注于特定细胞系，而不是精确的蛋白质目标。此外，使用这种筛选过程可以消除对现有药物治疗的已知蛋白质靶点的预先存在的偏见。这个平台可能会导致新药的发现，并扩大对其治疗潜力的理解。这个I-Corps项目利用体验式学习和对行业生态系统的第一手调查来评估该技术的翻译潜力。该解决方案基于高通量平台的开发，该平台能够发现异双功能蛋白质降解药物。该平台旨在整合高通量化学，直接生物学表型细胞毒性分析，二次毒性分析验证以及使用非活性药物类似物快速确认蛋白质降解。此外，该平台具有很强的适应性，可以应用于任何小分子、高通量的药物发现机构的筛选平台。这项技术可以让研究人员通过专注于特定的细胞系而不是蛋白质目标来识别降解药物，这是一类新的药物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This I-Corps project focuses on the development of a drug discovery platform to efficiently generate a new class of pharmaceutical drugs. The technology facilitates the generation of expansive drug libraries, enabling unbiased screening of observable characteristics. Importantly, this approach eliminates the need for prior knowledge of protein targets or specific chemicals. Using this platform, researchers can explore the vast landscape of potential drugs with the flexibility to focus on specific cell lines rather than exact protein targets. In addition, the use of this screening process may remove pre-existing bias towards known protein targets that may be treated with current drugs. This platform may lead to the discovery of novel drugs and expand the understanding of their therapeutic potential.This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. The solution is based on the development of a high-throughput platform that enables the discovery of heterobifunctional protein degrader drugs. The platform is designed to integrate high-throughput chemistry, direct-to-biology phenotypic cytotoxicity assays, validation in secondary toxicity assays, and rapid confirmation of protein degradation using inactive drug analogs. In addition, the platform is designed to be adaptable and can be implemented into any small-molecule, high-throughput screening platform utilized by institutions involved in drug discovery. The technology may allow researchers to identify degrader drugs, a new class of pharmaceuticals, by focusing on specific cell lines rather than protein targets.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.