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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)：拟议研究的总体目标是确定开发抗增殖剂SchweinFurtin家族的多形性胶质母细胞瘤等脑癌治疗方法的可行性。这些药物在体外对中枢神经系统来源的肿瘤细胞系具有高度毒性，更重要的是，似乎通过一个新的细胞靶点(S)表现出这种活性。施韦因富辛还含有促进脑血管屏障穿透的化学官能团，这是治疗原发性脑癌药物的一个非常重要的方面。这些研究的第一阶段由三个狭隘的目标组成，旨在证明寻找进步的可行性？来自该家族的治疗先导：这些目标包括：1)合成含有功能基团的施韦因呋喃西林类似物，旨在改善化合物的“类药物”性质；2)改进已发表的3-脱氧施韦因呋喃西林模体的六氢菲核心的合成方法，以便更高效、更安全地生产更多用于第二阶段研究的材料；以及3)旨在阐明施韦因呋喃西林的细胞或分子靶标的生物学研究。这些目标将使人们能够决定作为第二阶段的一部分，在临床前动物模型中进一步研究这些药物的可行性，并最终将基于这一独特且有效的化合物家族的药物用于抗脑癌。

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

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

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。