DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
批准号:
6300369
负责人:
LEON H. ZALKOW
金额:
$16.56万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-05-01 至 2000-08-31
关键词:
alkaloids analytical chemistry antineoplastics bioassay biological products biological signal transduction cell cycle proteins chemical fingerprinting chemical registry /resource chemical structure function combinatorial chemistry cooperative study drug design /synthesis /production drug screening /evaluation enzyme inhibitors flavones high performance liquid chromatography medicinal plants microorganism culture phosphatidylinositol 3 kinase phospholipase C phospholipase D plant extracts protein kinase yeasts
中文摘要
癌症可以被认为是一种细胞间信号改变的疾病。
这些研究的目标是识别和开发新的天然
产物对癌基因信号转导通路的抑制作用
癌症的治疗和预防。信令目标将是
包括磷脂信号转导酶(磷脂酰肌醇
磷脂酶C、磷脂酰肌醇-3-激酶和磷脂酶D),
蛋白丝氨酸/苏氨酸激酶(Raf-1、MEK和MAP-1)
和调节细胞周期的酶(cdc26磷酸酶和
CDK4激酶)。天然产品的来源将是用于
传统中药、美洲原住民药用植物、真菌
萃取物和天然产物的组合文库
分子(“前体”)。《中国》中确定的合作者将
经香港提供覆盖草药主要栖息地的植物
成长在中国身上。易于获得的天然产品,具有趣味性
生物活性,将作为“生物支架”来准备
产品的不同混合物(“前体”)通过使用非选择性
试剂、反应和/或反应条件。有效的销售线索将是
使用高性能生物测定定向指纹进行鉴定
对每一种粗提物或混合物进行高效液相色谱分离
“前体”,96孔微滴定板中的馏分,将被
已提交进行筛选。每一组分的指纹将会是
以二极管收集的紫外/可见光光谱的形式提供
阵列探测器,并存储在数据库中。论现役人员的认定
分数,原始参照板将被检索和质量
波谱和核磁共振等波谱数据将被收集在活跃的
威尔斯来完成指纹识别。这个指纹将被用来
重新收集所需的材料以进行进一步的提纯和测试
将通过最先进的方法在有机化合物中进行结构解析
化学反应。与已发现的活性化合物结构相似的化合物
将通过合成或在可行的情况下从其他来源获得,
已经检查过了。在生化反应中表现出活性的纯化合物
将对目标筛选的生长抑制活性进行评估
体外肿瘤细胞及体外活性较高的化合物
将在体内进行进一步的评估。前景看好的临床前研究进展
先导化合物将由我们的商业合作伙伴进行。
英文摘要
Cancer can be considered a disease of altered intercellular signalling.
The goal of these studies is to identify and develop novel natural
product inhibitors of oncogene signalling pathways for the effective
treatment and prevention of cancer. The signalling targets which will
be used include enzymes of phospholipid signaliing (phosphatidylinositol
phospholipase C, phosphatidylinositol-3-kinase and phospholipase D),
protein serine/threonine kinases (Raf-1 kinase, MEK kinase and MAP-
kinase) and enzymes that regulate the cell Cycle (cdc26 phosphatase and
cdk4 kinase). The sources of the natural products will be plants used in
traditional Chinese medicine, native Americans' medicinal plants, fungal
extracts, and combinatorial libraries of natural product derived
molecules ("progenomers"). Identified collaborators in China will
provide, via Hong Kong, plants which cover the major habitats of herbal
growth in China. Readily available natural products with interesting
biological activities, will be used as "biological scaffolds" to prepare
diverse mixtures of products ("progenomers") by use of non-selective
reagents, reaction and/or reaction conditions. Active leads will be
identified by bioassay-directed fingerprinting using high performance
liquid chromatography to obtain for each crude extract or mixture of
"progenomers", fractions in 96 well microtiter plates, which will be
submitted for screening. Fingerprints of each of these fractions will be
available in the form of ultraviolet/visible spectra collected by a diode
array detector and stored in a data bank. On identification of active
fractions, the original reference plate will be retrieved and mass
spectra and NMR and other spectral data will be collected on the active
wells to complete the fingerprinting. This fingerprint will be used to
recollect the desired material for further purification and testing
Structure elucidation will be done by state of the art methods in organic
chemistry. Compounds of analogous structures to those found to be active
will be obtained by synthesis or from other sources, where practical, and
screened. The pure compounds exhibiting activity in the biochemical
target screens will be evaluated for growth inhibitory activity against
tumor cells in vitro and those compounds of sufficient in vitro activity
will be further evaluated in vivo. Preclinical development of promising
lead compounds will be carried out by our commercial collaborator.
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DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
-
批准号:6102641
-
项目类别:
-
资助金额:$16.56万
-
财政年份:1999
-
负责人:LEON H. ZALKOW
-
依托单位:
DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
-
批准号:6269453
-
项目类别:
-
资助金额:$15.96万
-
财政年份:1998
-
负责人:LEON H. ZALKOW
-
依托单位:
DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
-
批准号:6237153
-
项目类别:
-
资助金额:$15.36万
-
财政年份:1997
-
负责人:LEON H. ZALKOW
-
依托单位:
SYNTHESIS OF CONGENERS & PRODRUGS
-
批准号:2357632
-
项目类别:
-
资助金额:$14.95万
-
财政年份:1996
-
负责人:LEON H. ZALKOW
-
依托单位:
SYNTHESIS OF CONGENERS & PRODRUGS
-
批准号:2682074
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1996
-
负责人:LEON H. ZALKOW
-
依托单位:
SYNTHESIS OF CONGENERS & PRODRUGS
-
批准号:6227623
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1996
-
负责人:LEON H. ZALKOW
-
依托单位:
SYNTHESIS OF CONGENERS & PRODRUGS
-
批准号:2631983
-
项目类别:
-
资助金额:$8.74万
-
财政年份:1996
-
负责人:LEON H. ZALKOW
-
依托单位:
SYNTHESIS OF CONGENERS & PRODRUGS
-
批准号:2852557
-
项目类别:
-
资助金额:$15.8万
-
财政年份:1996
-
负责人:LEON H. ZALKOW
-
依托单位:
IRREVERSIBLE ANTAGONISTS OF COCAINE AND OTHER STIMULANTS
-
批准号:3212959
-
项目类别:
-
资助金额:$21.53万
-
财政年份:1989
-
负责人:LEON H. ZALKOW
-
依托单位:
IRREVERSIBLE ANTAGONISTS OF COCAINE AND OTHER STIMULANTS
-
批准号:3212956
-
项目类别:
-
资助金额:$18.73万
-
财政年份:1989
-
负责人:LEON H. ZALKOW
-
依托单位:
IRREVERSIBLE ANTAGONISTS OF COCAINE AND OTHER STIMULANTS
-
批准号:3212960
-
项目类别:
-
资助金额:$22.87万
-
财政年份:1989
-
负责人:LEON H. ZALKOW
-
依托单位:
SEMISYNTHETIC PYRROLIZIDINE ALKALOID ANTITUMOR AGENTS
-
批准号:3169605
-
项目类别:
-
资助金额:$18.93万
-
财政年份:1982
-
负责人:LEON H. ZALKOW
-
依托单位:
SEMISYNTHETIC PYRROLIZIDINE ALKALOID ANTITUMOR AGENTS
-
批准号:3169606
-
项目类别:
-
资助金额:$18.47万
-
财政年份:1982
-
负责人:LEON H. ZALKOW
-
依托单位:
SEMISYNTHETIC PYRROLIZIDINE ALKALOID ANTITUMOR AGENTS
-
批准号:3169604
-
项目类别:
-
资助金额:$19.18万
-
财政年份:1982
-
负责人:LEON H. ZALKOW
-
依托单位:
DIVERSE NATURAL PRODUCTS FROM ISOLATION AND CHEMICAL MODIFICATION
-
批准号:5207663
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:LEON H. ZALKOW
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依托单位:--
海外基金