Novel Glioblastoma Therapeutics

胶质母细胞瘤新疗法

基本信息

批准号：
7218415
负责人：
JEFFREY D NEIGHBORS
金额：
$ 10.99万
依托单位：
TERPENOID THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2009-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7218415
关键词：
Alkylating Agents Animal Model Antineoplastic Agents Biological Biological Assay Biological Factors Blood - brain barrier anatomy Brain Cell Cycle Cell Line Central Nervous System Neoplasms Characteristics Chemicals Clinical Community Clinical Oncology Program Debridement Development Disease Drug Design Drug effect disorder Exhibits Family Feasibility Studies Glioblastoma Glioma Goals Heterocyclic Compounds In Vitro Incidence Individual Indoles Induction of Apoptosis Iowa Lead Malignant neoplasm of brain Malignant neoplasm of central nervous system Microarray Analysis Molecular Molecular Target Movement National Cancer Institute Nature New Agents Numbers Operative Surgical Procedures Outcome Patients Pattern Penetration Pharmaceutical Preparations Phase Production Publishing Radiation therapy Reaction Research Research Design Secure Series Standards of Weights and Measures Stilbenes Testing Therapeutic Therapeutic Intervention Time Tumor Cell Line Universities Variant analog base cellular targeting cerebrovascular chemotherapy design functional group improved in vivo indole novel outcome forecast pre-clinical temozolomide therapy development toxic metal tumor

项目摘要

DESCRIPTION (provided by applicant): The overall goal of the proposed studies is to establish the feasibility of developing therapies for brain cancers such as glioblastoma multiforme from the schweinfurthin family of antiproliferative agents. These agents are highly toxic to CNS derived tumor cell lines in vitro and more importantly appear to exhibit this activity via a novel cellular target(s). The schweinfurthins also contain chemical functional groups which should facilitate cerebrovascular barrier penetration, a very important aspect of drugs aimed at treating primary brain cancers. Phase One of these studies is comprised of three narrowly focused aims directed at proving the feasibility of finding advancing? a therapeutic lead from this family: These aims include: 1) synthesis of analogs of the schweinfurthins bearing functional groups designed to improve the "drug-like" nature of the compounds; 2) improvement of the published synthesis of the hexahydroxanthene core of the 3-deoxyschweinfurthin motif to allow for more efficient and safe production of larger quantities of material for Phase Two studies; and 3) biological studies aimed at elucidation of the cellular or molecular target of the schweinfurthins. These aims will allow a decision to be made about feasibility of studying these drugs further in pre-clinical animal models as part of Phase Two, and ultimately of bringing drugs based on this unique and potent family of compounds into use against brain cancer.

描述（由申请人提供）：拟议的研究的总体目标是建立从抗增殖剂的schweinfurthin家族中为脑癌（例如多形胶质母细胞瘤）开发疗法的可行性。这些药物在体外对CNS衍生的肿瘤细胞系有剧毒，更重要的是通过新颖的细胞靶标表现出这种活性。 Schweinfurthin还包含化学官能团，这些官能团应促进脑血管屏障渗透，这是旨在治疗原发性脑癌的药物的一个非常重要的方面。这些研究中的第一阶段由三个狭docusion的目的组成，旨在证明寻找前进的可行性？这个家族的治疗铅：这些目的包括：1）schweinfurthins具有官能团的类似物的合成，旨在改善化合物的“类似药物样”性质； 2）改善了3-脱氧素的六烷基核心已发表的合成，以使第二阶段研究更有效，更安全地生产大量材料； 3）旨在阐明schweinfurthins的细胞或分子靶标的生物学研究。这些目标将允许作为第二阶段的临床前动物模型中进一步研究这些药物的可行性，并最终将基于这种独特而有效的化合物系列的药物带入针对脑癌的使用。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

First total synthesis of (+)-Vedelianin, a potent antiproliferative agent.

首次全合成 ( )-Vedelianin，一种有效的抗增殖剂。

DOI：
10.1016/j.tetlet.2011.01.137
发表时间：
2011
期刊：
Tetrahedron letters
影响因子：
1.8
作者：
Topczewski,JosephJ;Wiemer,DavidF
通讯作者：
Wiemer,DavidF

Synthesis and biological activity of a fluorescent schweinfurthin analogue.

DOI：
10.1016/j.bmc.2009.04.071
发表时间：
2009-07-01
期刊：
Bioorganic & medicinal chemistry
影响因子：
3.5
作者：
Kuder CH;Neighbors JD;Hohl RJ;Wiemer DF
通讯作者：
Wiemer DF

Exploration of cascade cyclizations terminated by tandem aromatic substitution: total synthesis of (+)-schweinfurthin A.

通过串联芳族取代终止级联环化的探索：( )-schweinfurthin A 的全合成。

DOI：
10.1021/jo1022102
发表时间：
2011
期刊：
The Journal of organic chemistry
影响因子：
0
作者：
Topczewski,JosephJ;Kodet,JohnG;Wiemer,DavidF
通讯作者：
Wiemer,DavidF

Fluorescent schweinfurthin B and F analogs with anti-proliferative activity.

具有抗增殖活性的荧光 schweinfurthin B 和 F 类似物。

DOI：
10.1016/j.bmc.2010.07.056
发表时间：
2010
期刊：
Bioorganic & medicinal chemistry
影响因子：
3.5
作者：
Topczewski,JosephJ;Kuder,CraigH;Neighbors,JeffreyD;Hohl,RaymondJ;Wiemer,DavidF
通讯作者：
Wiemer,DavidF

Electrophilic aromatic prenylation via cascade cyclization.

通过级联环化进行亲电芳香族异戊二烯化。