PRECLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
PRECLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
批准号:
3853203
负责人:
E SAUSVILLE
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
蛋白激酶活性对蛋白激酶的作用具有明显的重要性。
多种生长因子和细胞癌基因。 因此,我们认为,
蛋白激酶活性中断可能导致新的治疗
剂. 已经研究了三类化合物,所有这些化合物都具有
已证实的抑制丝氨酸/苏氨酸或酪氨酸的能力
激酶。
AG 17和AG 592是厄布他汀的tyrphostin类似物。 这些化合物
都能抑制许多乳腺癌细胞系的生长,
IC 50约为0.5-5 μ m。 细胞生长的抑制并不
与已知的酪氨酸激酶活性的表达相关,
这组细胞系。
UCN-01和UCN-02,星形孢菌素的衍生物,抑制了
肺癌和前列腺癌细胞系,IC 50在0.1和1 μ m之间。
发现这些化合物具有广泛但非选择性的细胞毒性
在NCI-Developmental Therapeutics Program屏幕中,
化合物. 其生长抑制作用的机制并不
清楚
L 86 -8275是一种黄酮类化合物,已知其抑制EGF受体
激酶和cAMP依赖性激酶。 它抑制了乳房的生长
IC 50约为0.1 μ m的癌细胞系。 机械论
对这种化合物的研究表明,
在添加后8小时内合成DNA、RNA和蛋白质;
导致细胞周期G2期阻滞;其生长抑制
效果是可逆的。 因此,它的活性和效力使其
与其他先前描述的黄酮类化合物。
后续的研究将集中在是否上述生长抑制
作用与抑制激酶活性有关,
这些案件,以及是否有增加的活动,
常规细胞毒性剂通过这些化合物。
英文摘要
Protein kinase activity is of clear importance to the action of a
variety of growth factors and cellular oncogenes. Therefore,
interruption of protein kinase activity could lead to novel therapeutic
agents. Three classes of compounds have been studied, all of which have
the proven capacity to inhibit either serine/threonine or tyrosine
kinases.
AG17 and AG592 are tyrphostin analogs of erbstatin. These compounds
both inhibit the growth of a number of breast carcinoma cell lines with
IC50s of approximately 0.5-5 Um. The inhibition of cell growth does not
correlate with the expression of known tyrosine kinase activities in
this panel of cell lines.
UCN-01 and UCN-02, derivatives of staurosporin, inhibit the growth of
lung and prostate carcinoma cell lines, with IC50s between 0.1 and 1 Um.
These compounds were found to have broad but non-selective cytotoxicity
in the NCI-Developmental Therapeutics Program Screen for active
compounds. The mechanism of their growth-inhibitory effect is not
clear.
L86-8275 is a flavone with known capacity to inhibit both EGF-receptor
kinase and CAMP-dependent kinase. It inhibited growth of breast
carcinoma cell lines with IC50s of approximately 0.1 Um. Mechanistic
studies with this compound reveal that it inhibits macromolecular
synthesis of DNA, RNA, and protein within eight hours of addition; it
causes a block in the G2 phase of the cell cycle; its growth-inhibitory
effect is reversible. Thus, its activity and potency distinguishes it
from other previously described flavones.
Subsequent studies will focus on whether the above growth-inhibitory
effects are relatable to the inhibition of kinase activity in each of
these cases, and whether there is augmentation of activity of
conventional cytotoxic agents by these compounds.
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SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC
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批准号:3916617
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-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
IMMUNOTOXIN PROTOCOLS
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批准号:5201307
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC
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批准号:3939550
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
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批准号:3838151
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
TOXINS TARGETED TO THE CELL MEMBRANE--DISRUPTION OF SIGNAL TRANSDUCTION
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批准号:3752418
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
PRECLINICAL AND CLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
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批准号:3752419
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
G-PROTEIN EFFECTORS AS TARGETS FOR ANTINEOPLASTIC THERAPIES
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批准号:3774670
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
PROTEIN KINASE ANTAGONISTS--PRECLINICAL AND CLINICAL STUDIES
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批准号:2464490
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
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批准号:3774671
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
ENDOTHELIAL CELL TARGETED CANCER TREATMENT
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批准号:3752421
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
TOXINS TARGETED TO THE CELL MEMBRANE--DISRUPTION OF SIGNAL TRANSDUCTION
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批准号:5201344
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项目类别:
-
资助金额:$0.0万
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财政年份:--
-
负责人:E SAUSVILLE
-
依托单位:
PRECLINICAL AND CLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
-
批准号:5201345
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:E SAUSVILLE
-
依托单位:
G-PROTEIN EFFECTORS AS TARGETS FOR ANTINEOPLASTIC THERAPIES
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批准号:3838150
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:E SAUSVILLE
-
依托单位:
G-PROTEIN EFFECTORS AS TARGETS FOR ANTINEOPLASTIC THERAPIES
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批准号:3752420
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
-
依托单位:
TOXINS TARGETED TO THE CELL MEMBRANE--DISRUPTION IN SIGNAL TRANSDUCTION
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批准号:3838148
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
IMMUNOTOXIN PROTOCOLS--TARGETED THERAPY OF LYMPHOID NEOPLASMS
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批准号:6123682
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
TOXINS TARGETED TO THE CELL MEMBRANE--DISRUPTION IN SIGNAL TRANSDUCTION
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批准号:3774668
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
LINEAGE-SPECIFIC MARKER AND PROTO-ONCOGENE EXPRESSION IN HUMAN LUNG CANCER
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批准号:3939551
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
PRECLINICAL AND CLINICAL PHARMACOLOGY OF PROTEIN KINASE ANTAGONISTS
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批准号:3774669
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
SECOND MESSENGER AND RECEPTOR SYSTEMS IN HUMAN SCLC
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批准号:3963280
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:E SAUSVILLE
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依托单位:
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