NOVEL ASSAY PLATFORM FOR ASESSING PROTEIN KINASE INHIBITORS

描述（由申请人提供）：这个SBIR项目的目标是开发一个新的药物发现平台，用于筛选酪氨酸激酶抑制剂。该平台的主要创新之处在于使用多酶测定，能够在使用小体积样品的单个实验中实时测量效率并确定抑制机制。提出的平台通过将试剂成本降低十倍或更多，解决了现有方法的缺点；通过大幅度减少分析时间和显著提高药物筛选过程的信息产量。该技术适用于高通量put格式，具有识别和研究变构激酶抑制剂的独特能力，在开发治疗癌症、炎症性疾病、神经紊乱和代谢问题的新药物中发挥核心作用。公共卫生相关性：由于激酶在癌症、炎症性疾病、神经紊乱和代谢问题等病理状况中发挥重要作用，蛋白激酶代表了最有希望的药物靶标组之一。目前，所有用于药物发现和开发的研究支出中约有25%用于开发新的激酶抑制剂，其中特别关注的是发现变构抑制剂，这些抑制剂具有更高的抑制效率、更低的毒性和更长的作用时间。然而，鉴定新的变构抑制剂是具有挑战性的，需要繁琐的动力学和x射线衍射研究，这些研究成本高，劳动强度大，而且往往不能全面开展。该SBIR项目开发的技术具有识别和研究变链激酶抑制剂的独特能力，能够以更低的成本快速提供更多信息。

DESCRIPTION (provided by applicant): The goal of this SBIR project is to develop a new drug discovery platform for screening tyrosine kinase inhibitors. The main innovation of the proposed platform is the use of a multi-enzyme assay, which is able to measure efficiency and identify inhibition mechanism in a single experiment in real-time using a small-volume sample. The proposed platform addresses the drawbacks of the existing methods by reducing the cost of reagents by ten times or more; by substantially reducing the assay time and significantly increasing the information yield of the drug screening process. The technology is adaptable to high through put format and has unique capabilities for identification and study allosteric kinase inhibitors, which play a central role in the development of new pharmaceuticals for treatment of cancer, inflammatory diseases, neural disorders, and metabolism problems. PUBLIC HEALTH RELEVANCE: Protein kinases represent one of the most promising groups of drug targets due to the vital role played by kinases in such pathological conditions as cancer, inflammatory diseases, neural disorders, and metabolism problems. Currently about 25% of all research spending on drug discovery and development is directed to new kinase inhibitors with a special focus on the discovery of allosteric inhibitors, which have a higher inhibition efficiency, lower toxicity and longer duration of action. Yet, identification of new allosteric inhibitors is challenging and requires tedious kinetic and X-ray diffraction studies, which are costly, labor intensive and too often are not carried out at the full extend. The technology under development in this SBIR project has a unique capability for identification and study allosteric kinase inhibitors and is able to provide more information quickly and at a lower cost.