Combinatorial Chemical Libraries and Cancer Targets

该项目提出了小分子的识别，优化和表征， 影响Myc和β-连环蛋白-LEF网络中的蛋白质-蛋白质和蛋白质-DNA相互作用。 该项目还提出了从新化合物中鉴定和开发抗癌化合物的建议。 组合化学文库。这项工作是基于过去资助期间的发现 这些研究包括鉴定Myc-Max二聚化的第一个小分子抑制剂、LEF依赖性转录的抑制剂和干扰癌细胞生长的化合物。该项目依赖于与Boger博士实验室在化学领域以及与Cheresh博士在动物试验领域的密切合作。 具体目标如下： (1)鉴定和表征抑制Myc-Max二聚化的小分子。 (2)鉴定和表征稳定Myc网络蛋白相互作用的小分子。 (3)鉴定和表征特异性抑制LEF依赖性转录的小分子。 (4)筛选对癌细胞具有选择性活性的化合物的初级和模拟组合化学文库，并表征这些化合物。

This project proposes the identification, optimization, and characterization of small molecules that affect protein-protein and protein-DNA interactions in the Myc and the beta-catenin-LEF networks. The project also proposes identification and development of anticancer compounds from novel combinatorial chemical libraries. The work is based on discoveries made during the past funding cycle which include the identification of the first small molecule inhibitors of Myc-Max dimerization, inhibitors of LEF-dependent transcription, and compounds that interfere with the growth of cancer cells. The project depends on strong collaboration with the laboratory of Dr. Boger in the area of chemistry and with Dr. Cheresh in the area of animal testing. The following are the specific aims: (1) Identify and characterize small molecules that inhibit Myc-Max dimerization. (2) Identify and characterize small molecules that stabilize interaction of Myc network proteins. (3) Identify and characterize small molecules that specifically inhibit LEF-dependent transcription. (4) Screen primary and analog combinatorial chemical libraries for compounds that are selectively active against cancer cells and characterize these compounds.