Targeted Discovery of Marine-derived Anticancer Leads

海洋源性抗癌先导化合物的靶向发现

基本信息

批准号：
7934265
负责人：
Phil Crews
金额：
$ 27.31万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934265
关键词：
Targeted Discovery Marine derived Anticancer

项目摘要

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.

2004年，预计新诊断癌症病例将超过130万例，估计有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天然物质癌症化疗的产品领先。有五个实验室项目在封闭且运行的状态下运行协同时尚如下：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（该项目的 PI）领导 NCDDG），加州大学圣克鲁斯分校（UCSC）；实验室计划 #3 由 William Gerwick 教授领导，俄勒冈州立大学（OSU）；实验室项目 #4 由海洋学港口分部 Amy Wright 博士领导机构（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，加州大学圣地亚哥分校 (SIO-UCSD)。我们的总体目标如下。 (一)聘用初级 NIBRI 的表观遗传学和分子筛选指导这项研究的所有阶段。（二）利用学术资源旨在从海洋宏观和海洋中发现和表征新的、更有效的抗癌药物先导化合物的计划微生物。 (3) 将海洋生物的收集范围扩大到以前未勘探或勘探不足的地区海洋环境（例如深水、新领土、新类群），利用以下功能的强大组合 NCDDG 合作者的资源、经验和设备。 (4) 加速发现进程通过使用生物多样性海洋收藏品进行 LC 生成化学多样性峰库，以进行评估高通量筛选与光谱评估并行。 (5) 利用最先进的MS和NMR 去重复或结构解析技术。 (6) 使用药物化学、化学信息学和先导化合物优化的结构生物学后续研究。 (7) 进行高级临床前评价以确定具有对抗重要人类实体瘤（如乳腺癌、结肠癌、肺癌、卵巢癌）潜在效用的化合物和前列腺。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cryptosphaerolide, a cytotoxic Mcl-1 inhibitor from a marine-derived ascomycete related to the genus Cryptosphaeria.

DOI：
10.1021/np1000889
发表时间：
2010-05-28
期刊：
Journal of natural products
影响因子：
5.1
作者：
Oh H;Jensen PR;Murphy BT;Fiorilla C;Sullivan JF;Ramsey T;Fenical W
通讯作者：
Fenical W

The marine natural product microsclerodermin A is a novel inhibitor of the nuclear factor kappa B and induces apoptosis in pancreatic cancer cells.

DOI：
10.1007/s10637-014-0185-3
发表时间：
2015-02
期刊：
Investigational new drugs
影响因子：
3.4
作者：
Guzmán EA;Maers K;Roberts J;Kemami-Wangun HV;Harmody D;Wright AE
通讯作者：
Wright AE

Neopetrosiquinones A and B, sesquiterpene benzoquinones isolated from the deep-water sponge Neopetrosia cf. proxima.

Neopetrosiquinones A 和 B，从深水海绵 Neopetrosia 中分离出的倍半萜苯醌 cf.

DOI：
10.1016/j.bmc.2011.09.026
发表时间：
2011
期刊：
Bioorganic & medicinal chemistry
影响因子：
3.5
作者：
Winder,PriscillaL;Baker,HeatherL;Linley,Patricia;Guzmán,EstherA;Pomponi,ShirleyA;Diaz,MCristina;Reed,JohnK;Wright,AmyE
通讯作者：
Wright,AmyE

Structural and synthetic investigations of tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar marine cyanobacterium Lyngbya majuscula.

DOI：
10.1021/jo900578j
发表时间：
2009-08-07
期刊：
The Journal of organic chemistry
影响因子：
0
作者：
Gutiérrez M;Andrianasolo EH;Shin WK;Goeger DE;Yokochi A;Schemies J;Jung M;France D;Cornell-Kennon S;Lee E;Gerwick WH
通讯作者：
Gerwick WH

Biologically active new metabolites from a Florida collection of Moorea producens.