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）：尽管近乎全面的怀疑主义最初向Folkman提出了他对抗血管生成的看法，即抗血管生成将是一种有效的癌症化疗方法，但该概念现在已被广泛接受，不仅构成了癌症治疗的基础，不仅是癌症治疗的基础，而且还用于对非封存的范围进行广泛的范围，该范围众多的习惯是及时习惯的既定范围，既既依赖又有符合的范围。目前，针对与血管生成有关的中心化学物质的批准疗法是有用的，但不是完全安全或有效的。我们建议通过强大的噬菌体显示方法发现新的抗VEGF代理，并将这些新药物作为即将产生的安全有效的血管生成抑制剂。我们的具体目的是：（i）发现和开发针对VEGF受体家族的新型抗血管生成型肽型化合物，以及（ii）设计和测试新药物以控制视网膜血管生成。这些药物都将有选择地与病理新血管结合并阻止或破坏它们，而不会影响正常的血管。我们的目标是理解和抑制引起人失明疾病的实验小鼠模型的神经视网膜病理性血管生成。

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