SCREENING TECHNOLOGY FOR CANCER THERAPEUTICS

癌症治疗筛选技术

• 批准号: 2008862
• 负责人: GRANT A. BITTER
• 金额: $ 39.02万
• 依托单位: BITTECH, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2008862
• 关键词: Saccharomyces cerevisiae; antineoplastics; bioassay; biotechnology; cell cycle proteins; cell growth regulation; cell line; cyclins; drug screening /evaluation; enzyme activity; fungal genetics; gene deletion mutation; genetic regulation; method development; molecular cloning; phenotype; protein kinase; protein structure function; reporter genes

It has long been understood that cancer cells have lost normal cellular growth control. Recent research has demonstrated a correlation between specific defects in cell cycle regulation and a variety of cancers. During Phase I of this SBIR grant, BitTech, Inc. developed in vivo phenotypic screens for cyclin/cyclin dependent kinase (cyclin/CDK) function. Cyclin/CDKs are the key regulators of eukaryotic cell cycle control, and three reporter genes were placed under control of a promoter which is regulated by a specific cyclin/CDK. Phase I research further demonstrated the feasibility of using the BitTech core technology for measuring effects on cyclins, CDKs or CDK inhibitor proteins (CKIs). During Phase II, the core technology will be further developed for use in targeted screening programs. Cell lines will be generated in which human cell cycle regulatory proteins, which are known to be mutant or aberrantly regulated in specific cancers, are incorporated as the molecular targets in the phenotypic screens. The test material for these high throughput screens may be expressed cDNA from various cell types, existing chemical libraries, new combinatorial libraries or products of rational design programs. Because these compounds will be discovered in screens which are highly specific for proteins which are mutant or aberrantly regulated in cancer cells, they (or analogues developed from the lead compound) are expected to exhibit improved efficacy and reduced side effects for the patients, compared to currently available therapies. PROPOSED COMMERCIAL APPLICATION Current cancer therapies are frequently ineffective and have significant side effects for the patient. The in vivo screens for cyclin/CDK function are targeted to the key cell cycle regulatory proteins which are defective in certain cancers. Therefore, therapeutic compounds discovered with this technology are expected to exhibit improved efficiency and reduced side effects for the patient. Such therapies will decrease cancer-associated morbidity and health care costs.

长期以来，人们一直认为癌细胞已经失去了正常的细胞， 生长控制 最近的研究表明， 细胞周期调控中的特定缺陷和各种 癌的 在SBIR赠款的第一阶段，BitTech，Inc.发达 细胞周期蛋白/细胞周期蛋白依赖性激酶体内表型筛选 （cyclin/CDK）功能。 细胞周期蛋白/CDK是细胞周期的关键调节因子， 真核细胞周期控制，并将三个报告基因 在由特定的启动子调控的启动子的控制下， 细胞周期蛋白/CDK。 第一阶段研究进一步证明了 使用BitTech核心技术测量对细胞周期蛋白的影响， CDK或CDK抑制蛋白（CKI）。 在第二阶段，核心 将进一步开发用于靶向筛查的技术 程序. 细胞系将在人类细胞周期中产生 调节蛋白，其已知是突变的或异常的， 在特定的癌症中调节，作为分子靶点， 在表型筛选中。 这些高通量的测试材料 筛选可以表达来自各种细胞类型的cDNA，现有的 化学库、新的组合库或理性的产品 设计方案。 因为这些化合物将在 筛选对突变蛋白或 在癌细胞中受到异常调节，它们（或从 先导化合物）预期表现出改善的功效， 与目前可用的相比，减少了患者的副作用 治疗 建议的商业应用 目前的癌症治疗通常无效，并且具有显著的 对病人的副作用。 cyclin/CDK的体内筛选 功能是针对关键的细胞周期调控蛋白， 在某些癌症中有缺陷。 因此，治疗化合物 使用这种技术发现的， 效率和减少的副作用。 这些疗法将 降低癌症相关的发病率和卫生保健费用。