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

• 批准号: 8752696
• 负责人: RENATA PASQUALINI
• 金额: $ 23万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8752696
• 关键词: Targeted; Modulation; Angiogenesis; VEGFR; Peptidomimetic

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：尽管最初对Folkman提出的抗血管生成将是癌症化疗的有效方法的想法几乎普遍持怀疑态度，但这一概念现在已被广泛接受，不仅形成了癌症治疗的基础，而且还形成了Folkman在术语“血管生成依赖性疾病”下总结的广泛的非肿瘤性疾病的治疗基础。目前批准的针对参与血管生成的中心身体化学物质VEGF的疗法是有用的，但并不完全安全或有效。我们建议通过强大的噬菌体展示方法开发新的抗VEGF药物，并将这些新药物作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）发现和开发靶向VEGF受体家族的新的抗血管生成肽模拟物化合物，和（ii）设计和测试用于治疗性控制视网膜血管生成的新试剂。这两种药物都能选择性地与病理性新血管结合，并阻断或破坏它们，而不影响正常血管。我们的目标是了解和抑制病理性血管生成的实验小鼠模型的人类致盲性疾病的神经视网膜。

项目成果

The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease.

• DOI: 10.1126/scitranslmed.aac4882
• 发表时间: 2015-10-14
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Sidman RL;Li J;Lawrence M;Hu W;Musso GF;Giordano RJ;Cardó-Vila M;Pasqualini R;Arap W
• 通讯作者: Arap W