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Enzyme Assay Chips for Apoptosis Discovery

用于细胞凋亡发现的酶检测芯片

基本信息

批准号：
7119670
负责人：
HAICHING MA
金额：
$ 35.07万
依托单位：
REACTION BIOLOGY CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-10 至 2007-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Reaction Biology Corporation has developed an extremely low cost nanoliter reaction microarrays to serve markets for ultra high throughput screening (uHTS) drug discovery, large scale IC50 determinations, and large scale IC50 selectivity/toxicity profiling. These reactions are 1000 to 10,000-fold smaller than well plate formats used widely in drug discovery. Currently, 3072 drug screening reactions can be carried out on a single microarray. During Phase I, Reaction Biology demonstrated that: purified human caspases have robust activities under the reaction conditions of the chip and can be quantitatively measured using the Reaction Biology enzyme chip technology. Through Phase I, RBC has demonstrated feasibility in creating controllable and cost effective caspase chips. Specific Aim 1 involves the validation of caspase assays on microarrays for IC50 profiling and uHTS using a small "standardization" library. Specific Aim 2 involves the screening of two different chemical libraries (totaling 175,000 compounds) against all 10 human caspases. All hits will be verified by measurement of IC50 on the microarrays. Finally, Specific Aim 3 involves the testing of hits in well plate assays against purified caspases and in a cell-based assay of apoptosis. New inhibitors of caspases may lead to advances in the treatment of neurodegenerative processes during acute injury or in chronic disease.

描述（由申请人提供）：Reaction Biology Corporation开发了一种成本极低的纳升反应微阵列，用于超高通量筛选（uHTS）药物发现、大规模IC 50测定和大规模IC 50选择性/毒性分析。这些反应比药物发现中广泛使用的孔板形式小1000至10，000倍。目前，3072个药物筛选反应可以在单个微阵列上进行。在第一阶段，Reaction Biology证明：纯化的人caspase在芯片的反应条件下具有稳健的活性，并且可以使用Reaction Biology酶芯片技术进行定量测量。通过第一阶段，RBC已经证明了创造可控和成本效益的caspase芯片的可行性。具体目标1涉及使用小的“标准化”文库在用于IC 50谱和uHTS的微阵列上验证半胱天冬酶测定。特定目标2涉及针对所有10种人类半胱天冬酶筛选两个不同的化学库（总计175，000种化合物）。所有命中将通过测量微阵列上的IC 50进行验证。最后，特异性目标3涉及在孔板试验中针对纯化的半胱天冬酶和基于细胞的细胞凋亡试验中检测命中。新的半胱天冬酶抑制剂可能会导致急性损伤或慢性疾病期间神经退行性过程的治疗进展。