Phosphorylated Form of Activated IKKbeta and Pancreatic Cancer

磷酸化形式的活化 IKKbeta 与胰腺癌

基本信息

批准号：
8777952
负责人：
Amarnath Natarajan
金额：
$ 19.64万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8777952
关键词：
Address Adverse effects Animal Model Animals Antibodies Apoptosis Autopsy Blood capillaries Cancer Patient Cancer cell line Cessation of life Chronic Clinic Data Development Diagnosis Disease Drug Targeting Ductal Epithelial Cell Embryo Endotoxins Event Genetic study Goals Growth Health Human Immune response Immunohistochemistry Infection Inflammatory Isoelectric Focusing Label Lipopolysaccharides Malignant neoplasm of pancreas Mediating Metastatic Neoplasm to the Liver Modeling Mus Mutate Mutation Normal Cell Normal tissue morphology Pancreas Pancreatic Ductal Adenocarcinoma Pathology Patients Pharmaceutical Preparations Pharmacologic Substance Phospho-Specific Antibodies Phosphorylation Phosphotransferases Post-Translational Protein Processing Predisposition Protein Dephosphorylation Proteins Research Project Grants Sampling Specimen Stimulus Survival Rate System TNF gene Technology Testing Therapeutic Therapeutic Intervention Tissues Toxic effect Tumor Cell Line base cancer therapy capillary inhibitor/antagonist innovation kidney cell kinase inhibitor mortality mutant neoplastic cell new technology novel overexpression pancreatic cancer cells pancreatic neoplasm pre-clinical programs small molecule therapeutic target therapy resistant tumor tumor growth tumor microenvironment tumorigenesis

项目摘要

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.

描述（由申请人提供）：正如 FDA 最近批准用于癌症治疗的激酶抑制剂的数量所证明的那样，激酶是有吸引力的药物靶标，目前临床上的药物针对的是过度表达的激酶或与疾病无关的突变激酶。所有可药物激酶在许多情况下都发生突变或过度表达，它们的活性通过翻译后修饰而改变，我们还发现磷酸化 IKK 水平升高。与正常组织相比，肿瘤样本中的 IKK 的患病状态存在磷酸化状态。与其他激酶一样，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 的磷酸特异性抗体。使得定义疾病状态成为一项具有挑战性的工作，在本应用中，我们将使用新技术 NanoPro 1000 来解决胰腺肿瘤和细胞系中的这个问题，因为我们试图表征与胰腺肿瘤和细胞系相关的各种翻译后修饰。我们关注 IKK 的特定形式。，而不是 IKK¿总的来说，这使得这个麻烦变得新颖和创新。