Targeted Discovery of Marine-derived Anticancer Leads

2004年，预计将有130多万新癌症病例被诊断出来， 美国人会死于这种疾病。我们的NCDDG计划的总体目标是发现海洋自然 癌症化疗的产品领导者。有五个实验室项目在封闭的环境中运行， 协同方式如下：Novartis Institutes of Biomedical Research，Inc.的实验室项目#1。 （NIBRI），由执行董事Dennis France领导;实验室项目#2由菲利普克鲁斯教授（该项目的PI）领导 NCDDG），加州大学，圣克鲁斯（UCSC）;实验室计划#3由William Gerwick教授领导， 俄勒冈州州立大学（OSU）;实验室项目#4，由港口分支海洋学Amy Wright博士领导 研究所（HBOI）;实验室计划#5由斯克里普斯海洋研究所的William Fenical教授领导， 加州圣地亚哥大学（SIO-UCSD）。我们的总体目标如下。(1)雇用主要的 在NIBRI的表观遗传和分子筛选，以指导这项研究的所有阶段。(2)利用学术 计划发现和表征新的，更有效的抗癌药物，从海洋宏观和 微生物的(3)将海洋生物的收集范围扩大到以前未开发或开发不足的地区 海洋环境（例如，深水、新界、新分类群）， NCDDG合作者的资源、经验和设备。(4)为了加快发现过程 通过使用生物多样性海洋收集物用于LC生成化学多样性峰库， 高通量筛选与光谱评估并行进行。(5)利用最先进的质谱和核磁共振技术 用于去复制或结构解析的技术。(6)使用药物化学，化学信息， 结构生物学随访以优化电极导线。(7)进行高级临床前评价，以确定 对重要的人实体瘤如乳腺、结肠、肺、卵巢癌具有潜在效用的化合物 和前列腺

In 2004, it is expected that over 1.3 million new cancer cases will be diagnosed and an estimated 563,700 Americans will die of this disease. The overall goal of our NCDDG program is to discover marine natural product leads for cancer chemotherapy. There are five laboratory programs operating in a close and synergistic fashion as follows: Lab Program #1 at the Novartis Institutes of Biomedical Research, Inc. (NIBRI), led by Executive Director Dennis France; Lab Program #2 led by Prof. Phillip Crews (PI of this NCDDG), University of California, Santa Cruz (UCSC); Lab Program #3 led by Prof. William Gerwick, Oregon State University (OSU); Lab Program #4 led by Dr. Amy Wright, Harbor Branch Oceanographic Institution (HBOI); and Lab Program #5 led by Prof. William Fenical, Scripps Institution of Oceanography, University of California San Diego (SIO-UCSD). Our overall aims are as follows. (1) To employ the primary epigenetic and molecular screens at NIBRI to guide all phases of this research. (2) To utilize the academic programs to discover and characterize new, more effective anticancer drug leads from marine macro- and microorganisms. (3) To expand the collection of marine organisms to previously unexplored or underexplored ocean environments (e.g., deep water, new territories, new taxa) using the powerful combination of resources, experience, and equipment of the NCDDG collaborators. (4) To accelerate the discovery process by using biodiverse marine collections for the LC generation of chemodiverse peak libraries for evaluation in high throughput screens in parallel with spectroscopic evaluation. (5) To utilize state-of-the-art MS and NMR techniques for dereplication or structure elucidation. (6) To use medicinal chemical, chemoinformatic, and structural biological follow-up for lead optimization. (7) To conduct advanced preclinical evaluation to identify compounds with potential utility against important human solid tumors such as breast, colon, lung, ovarrian and prostate.