Phosphorylated Form of Activated IKKbeta and Pancreatic Cancer

描述（由申请人提供）：激酶是有吸引力的药物靶点，最近FDA批准的用于癌症治疗的激酶抑制剂的数量证明了这一点。目前在诊所使用的药物是针对过度表达的激酶或与该疾病有关的突变激酶。然而，并非所有的可药物激酶都发生突变或过表达，在许多情况下，它们的活性通过翻译后修饰而改变。与正常组织相比，其他人和我们已经发现肿瘤样本中磷酸化的IKK¿水平升高，这表明IKK¿存在磷酸化状态。像其他激酶一样，IKK¿受连续磷酸化-去磷酸化事件的调节。缺乏针对各种磷酸化形式的IKK¿的磷酸化特异性抗体使得定义患病状态成为一项具有挑战性的努力。在这个应用中，我们将使用一种新技术NanoPro 1000来解决胰腺肿瘤和细胞系的这个问题。这是一个探索性项目，因为我们试图描述与疾病相关的激酶相关的各种翻译后修饰。我们专注于IKK¿的具体形式，而不是一般的IKK¿，这使得这个麻烦新颖和创新。

DESCRIPTION (provided by applicant): Kinases are attractive drug targets as evidenced by the number of recent FDA approvals of kinase inhibitors for cancer therapy. The drugs currently in the clinics are against either overexpressed kinases or mutated kinases that are implicated in the disease. However not all druggable kinases are mutated or overexpressed in many cases their activity altered through post-translational modifications. Others and we have identified elevated levels of phosphorylated IKK¿ in the tumor samples compared to the normal tissues suggesting that the diseased state of IKK¿ exists phosphorylated state. IKK¿ like other kinases is regulated by sequential phosphorylation-dephosphorylation events. The lack of phospho-specific antibodies against the various phosphorylated forms of IKK¿ makes defining the diseased state a challenging endeavor. In this application we will use a novel technology NanoPro 1000 to address this issue in pancreatic tumors and cell lines. This is an exploratory project as we seek to characterize the various post-translational modifications associated with a disease relevant kinase. Our focus on the specific forms of IKK¿, rather than IKK¿ in general, makes this bother novel and innovative.