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SCREENING TECHNOLOGY FOR CANCER THERAPEUTICS

癌症治疗筛选技术

基本信息

批准号：
2633906
负责人：
GRANT A. BITTER
金额：
$ 50.97万
依托单位：
BITTECH, INC.
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-05-01 至 2000-12-31
项目状态：
已结题

项目摘要

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.

人们很早就知道癌细胞已经失去了正常细胞生长控制。最近的研究表明了相关性细胞周期调节的特定缺陷与各种癌症。在 SBIR 拨款的第一阶段期间，BitTech, Inc. 开发了细胞周期蛋白/细胞周期蛋白依赖性激酶的体内表型筛选（细胞周期蛋白/CDK）功能。细胞周期蛋白/CDK 是关键调节因子真核细胞周期控制，放置三个报告基因在受特定调节的启动子的控制下细胞周期蛋白/CDK。一期研究进一步证明了可行性使用 BitTech 核心技术测量对细胞周期蛋白的影响， CDK 或 CDK 抑制剂蛋白 (CKI)。在第二阶段，核心将进一步开发技术用于靶向筛选程序。将产生细胞系，其中人类细胞周期调节蛋白，已知是突变或异常的在特定癌症中受到调节，被纳入分子靶标在表型屏幕中。这些高通量的测试材料筛选可以从各种细胞类型中表达 cDNA，现有的化学库、新的组合库或理性产品设计程序。因为这些化合物将被发现于对突变或突变蛋白质具有高度特异性的筛选在癌细胞中受到异常调节，它们（或从先导化合物）预计将表现出改进的功效，并且与目前可用的相比，减少了患者的副作用疗法。拟议的商业应用目前的癌症治疗常常无效并且具有显着的效果对患者产生副作用。细胞周期蛋白/CDK 的体内筛选功能针对关键的细胞周期调节蛋白某些癌症有缺陷。因此，治疗化合物用这项技术发现的预计会表现出改进效率并减少患者的副作用。此类疗法将降低癌症相关发病率和医疗费用。