Inhibitors of p90Rsk

描述(由申请人提供)：这项工作的长期目标包括发展对丝裂原活化蛋白激酶(MAPK)途径中丝氨酸/苏氨酸蛋白激酶RSK家族在信号转导中的作用(S)的了解，以及识别新类别的潜在抗肿瘤药物。近期目标包括-化学合成一组被证明可介导对RSK2的高度选择性抑制的山奈酚糖苷类似物-通过电子筛选从NCI资料库中鉴定出第二类抑制剂的类似物-鉴定其他具有不同类型化学结构和性质的P90 RSK天然抑制剂这项工作与公众健康有关，因为一种有效的和选择性的RSK抑制剂很可能显示出对某些癌症，尤其是乳腺癌的治疗有效的活性。

DESCRIPTION (provided by applicant): The long term goals of this work include the development of an understanding of the role(s) of the ser/thr protein kinase Rsk family in signal transduction within the mitogen-activated protein kinase (MAPK) pathway, and the identification of new classes of potential antitumor agents. The immediate objectives include - chemical synthesis of analogues of a group of kaempferol glycosides shown to mediate highly selective inhibition of Rsk2 - synthesis of analogues of a second class of inhibitors identified from the NCI repository by in silico screening - identification of additional naturally occurring inhibitors of p90 Rsk that have different types of chemical structures and properties This work is relevant to public health in that a potent and selective Rsk inhibitor is likely to exhibit activity useful for the treatment of certain cancers, notably breast cancer.