Targeted Discovery of Marine-derived Anticancer Leads

2004年，预计将诊断出130多万新的癌症病例，估计为563,700例 美国人将死于这种疾病。我们NCDDG计划的总体目标是发现海洋自然 为癌症化疗提供产品线索。有五个实验室项目正在结束运行， 协同方式如下：诺华生物医学研究所的实验室计划#1。 (NIBRI)，由执行董事Dennis France领导；实验室计划#2，由Phillip Crews教授(PI of This NCDDG)，加州大学圣克鲁斯分校(UCSC)；由William Gerwick教授领导的实验计划#3 俄勒冈州立大学(OSU)；由海港海洋分校艾米·赖特博士领导的实验室计划#4 斯克里普斯海洋研究所(HBOI)；以及由斯克里普斯海洋研究所威廉·费尼奇教授领导的实验室计划#5， 加州大学圣地亚哥分校(SIO-UCSD)。我们的总体目标如下。(一)聘用小学 NIBRI的表观遗传学和分子筛查指导这项研究的所有阶段。(2)充分利用学术力量 从海洋宏观和微观结构中发现和表征新的、更有效的抗癌药物线索的计划 微生物。(3)将海洋生物的采集范围扩大至以前未开发或未开发的海洋生物 海洋环境(例如，深水、新领地、新类群) NCDDG合作者的资源、经验和设备。(四)加快发现进程 通过使用生物多样性海洋生物样品进行LC生成化学多样性峰文库以供评估 与光谱评估并行的高通量筛选。(5)利用最先进的MS和核磁共振技术 去复制或结构阐明的技术。(六)使用药用化学品、化学信息剂和 铅优化的结构生物学跟踪。(7)进行高级临床前评估，以确定 对乳腺、结肠、肺、卵巢等人体重要实体肿瘤有潜在疗效的化合物 和前列腺癌。

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.