NOVEL ASSAY PLATFORM FOR ASESSING PROTEIN KINASE INHIBITORS

用于评估蛋白激酶抑制剂的新型检测平台

• 批准号: 7745795
• 负责人: Val V. Golovlev
• 金额: $ 10.03万
• 依托单位: SCI-TEC, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7745795
• 关键词: Address; Biological Assay; Development; Disease; Drug Delivery Systems; Enzymes; Goals; Inflammatory; Kinetics; Malignant Neoplasms; Measures; Metabolic Diseases; Methods; Pharmacologic Substance; Phosphotransferases; Play; Preclinical Drug Evaluation; Process; Protein Kinase; Protein Kinase Inhibitors; Reagent; Research; Role; Sampling; Screening procedure; Small Business Innovation Research Grant; Technology; Time; Toxic effect; Tyrosine Kinase Inhibitor; X ray diffraction analysis; X-Ray Diffraction; cancer therapy; cost; drug discovery; inhibitor/antagonist; innovation; kinase inhibitor; novel; protein kinase inhibitor; public health relevance; relating to nervous system; research study; time use

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.

描述（由申请人提供）：该 SBIR 项目的目标是开发用于筛选酪氨酸激酶抑制剂的新药物发现平台。该平台的主要创新是使用多酶测定，它能够使用小体积样品在单次实验中实时测量效率并识别抑制机制。所提出的平台通过将试剂成本降低十倍或更多来解决现有方法的缺点；通过大幅减少检测时间并显着提高药物筛选过程的信息产量。该技术适用于高通量形式，并具有识别和研究变构激酶抑制剂的独特能力，在开发用于治疗癌症、炎症性疾病、神经疾病和代谢问题的新药物中发挥着核心作用。公共健康相关性：蛋白激酶代表了最有前途的药物靶点之一，因为激酶在癌症、炎症性疾病、神经疾病和代谢问题等病理状况中发挥着至关重要的作用。目前，大约25%的药物发现和开发研究支出用于新的激酶抑制剂，特别是变构抑制剂的发现，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持续时间。然而，新变构抑制剂的鉴定具有挑战性，需要繁琐的动力学和 X 射线衍射研究，这些研究成本高昂、劳动强度大，而且往往无法充分进行。该SBIR项目正在开发的技术具有识别和研究变构激酶抑制剂的独特能力，并且能够以更低的成本快速提供更多信息。