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Targeted Modulation of Angiogenesis by VEGFR Peptidomimetic Antagonists

VEGFR 肽模拟拮抗剂对血管生成的靶向调节

基本信息

批准号：
8271409
负责人：
RENATA PASQUALINI
金额：
$ 14.35万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8271409
关键词：
Adult Affect Age related macular degeneration Agonist Angiogenesis Inhibitors Animal Model Apoptosis Inhibitor Arthritis Asthma Bacteriophages Binding Biological Assay Blindness Blood Vessels Chemicals Chemotherapy-Oncologic Procedure Cirrhosis Databases Development Diabetes Mellitus Diabetic Retinopathy Disease Drug Delivery Systems Embryonic Development Endothelial Cells Experimental Models Family Female Generations Genes Goals Grant Growth Human In Vitro Ligand Binding Ligands Literature Macular degeneration Malignant Neoplasms Mediating Methods Modeling Molecular Mus Neural Retina Neuropilin-1 New Agents Nutrient Obesity Organ Oxygen Pathologic Neovascularization Pathway interactions Peptide Receptor Peptide Transport Peptides Phage Display Pharmaceutical Preparations Process Retina Retinal Retinal Diseases Retinopathy of Prematurity Role Screening procedure Series Testing Therapeutic Time Tissues Toxin Treatment Protocols United States Food and Drug Administration Vascular Diseases Vascular Endothelial Cell Vascular Endothelial Growth Factor Receptor Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factors Wound Healing angiogenesis antiangiogenesis therapy base cancer therapy design design and construction drug candidate expectation in vivo insight molecular marker mouse model novel peptidomimetics prevent prototype receptor reproductive retina blood vessel structure retinal angiogenesis tumor

项目摘要

Despite the near-universal skepticism that initially greeted Folkman¿s presentation of his idea that anti-angiogenesis would be an effective approach to cancer chemotherapy, this concept has now become widely accepted and forms a basis not only for cancer therapy, but also for therapy of a broad range of non-neoplastic disorders that Folkman summarizes under the term 'angiogenesis-dependent diseases'. Currently approved therapies, directed against the central bodily chemical involved in angiogenesis, VEGF, are useful, but not entirely safe or effective. We propose to develop new anti-VEGF agents through discovery by powerful phage display methods, and to apply these new agents as a forthcoming generation of safe and effective angiogenesis inhibitors. Our specific aims are: (i) to discover and develop new anti-angiogenic peptidomimetic compounds targeting the VEGF receptor family, and (ii) to design and test new agents for therapeutic control of retinal angiogenesis. These agents would both bind selectively to pathological new blood vessels and block or destroy them, without affecting normal blood vessels. Our goal is to understand and inhibit pathological angiogenesis in the neural retina of experimental mouse models of human blindness-causing diseases.

尽管最初受到福克曼的几乎普遍的怀疑，S提出了他的抗血管生成的想法将是一种有效的癌症化疗方法，这一概念现在已得到广泛应用不仅是癌症治疗的基础，也是广泛的非肿瘤治疗的基础 Folkman将疾病概括为“血管生成依赖型疾病”。目前已批准针对参与血管生成的中枢身体化学物质血管内皮生长因子的治疗是有效的，但不是完全安全或有效的。我们建议通过发现强大的噬菌体来开发新的抗血管内皮生长因子药物展示方法，并将这些新制剂应用为下一代安全有效的血管生成抑制剂。我们的具体目标是：(I)发现和开发新的抗血管生成多肽以血管内皮生长因子受体家族为靶点的化合物，以及(Ii)设计和测试用于治疗控制糖尿病的新药物视网膜血管生成。这些药物都会选择性地与病理性新血管结合，并阻断或在不影响正常血管的情况下摧毁它们。我们的目标是了解和抑制病理性人类致盲疾病实验模型小鼠视网膜神经中的血管生成。