Chemistry and Cancer Scientific Program

项目总结（见说明）： 化学与癌症计划（CCP）旨在发现能够 拮抗或激动与人类癌症相关的调节途径。中共的研究工作 从化学到生物学或生物学到化学这两个方向中的一个进行。在前一种情况下， 发现过程始于一种对癌细胞具有细胞毒性的新型天然产物。这个分子， 由有机化学家合成的特定衍生物，然后进行生物化学，遗传学或分子生物学， 生物学研究旨在解决其精确的作用模式。或者，了解特定的 与人类癌症相关的生物学途径促使人们尝试鉴定小的化学拮抗剂， 途径的激动剂。后一种途径是通过高通量药物筛选， 肽模拟物或生物代谢物的合成类似物的制备。在这方面，目前 科学方案的主题是： 1)识别新型细胞毒性剂的分子靶点。 2)小说的生化剖析。癌细胞特异性途径。 3)合成化学物质干扰细胞凋亡的模拟物和其他方法。 4)用小分子调节和靶向缺氧反应途径。 中共的长期目标是发现

PROJECT SUMMARY (See instructions): The Chemistry and Cancer Program (CCP) seeks to discover small molecule chemicals capable of either antagonizing or agonizing regulatory pathways relevant to human cancer. Research efforts in the CCP proceed from one of two directions, chemistry-to-biology or biology-to-chemistry. In the former case, the discovery process starts with a novel natural product that is cytotoxic to cancer cells. This molecule, and specific derivatives synthesized by organic chemists, is then subjected to biochemical, genetic or molecular biological studies aimed at resolving its precise mode of action. Alternatively, knowledge of a specific biological pathway relevant to human cancer prompts attempts to identify small chemical antagonists or agonists of the pathway. The latter path is prosecuted by high throughput drug screening, rafional peptidomimetics, or preparation of synthetic analojgs of biological metabolites. In this context, the current scientific program themes are: 1) Identifying the Molecular Targets of Novel Cytotoxic Agents. 2) Biochemical Dissection of Novel. Cancer Cell-Specific Pathways. 3) Smac mimetics and other means of perturbing apoptosis with synthetic chemicals. 4) Regulation and targeting of the hypoxia response pathway with small molecules. The long-term objective of the CCP is to discover