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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.

尽管福克曼提出的抗血管生成的想法最初受到了几乎普遍的怀疑，将是一种有效的方法，癌症化疗，这一概念现在已成为广泛它不仅是癌症治疗的基础，而且也是广泛的非肿瘤性疾病治疗的基础。 Folkman将其总结为“血管生成依赖性疾病”。目前批准针对参与血管生成的中心身体化学物质VEGF的治疗是有用的，但完全安全或者有效。我们建议开发新的抗VEGF药物通过发现强大的噬菌体显示方法，并应用这些新的代理作为下一代的安全和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肽模拟物靶向VEGF受体家族的化合物，和（ii）设计和测试用于治疗性控制VEGF受体家族的新试剂。视网膜血管生成这些药剂将选择性地结合病理性新血管并阻断或破坏它们，而不影响正常的血管。我们的目标是了解和抑制病理性的在人类致盲性疾病的实验小鼠模型的神经视网膜中的血管生成。