Engineering vascularized tissues using natural and synthetic small molecules
Engineering vascularized tissues using natural and synthetic small molecules
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DOI：
10.4161/org.4.4.6963
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发表时间：
2008-10
期刊：
影响因子：
2.3
通讯作者：
L. S. Sefcik;C. E. Petrie Aronin;E. Botchwey
中科院分区：
文献类型：
--
作者：
L. S. Sefcik;C. E. Petrie Aronin;E. Botchwey
血管生长和重塑是一个复杂的过程，依赖于许多不同的信号分子的适当的空间和时间调节，以形成功能性血管网络。理解和调节这些信号的能力是重要的临床需求，具有治疗各种疾病病理的潜力。目前的方法主要集中在递送蛋白质以促进缺血组织的新血管形成，最显著的是VEGF和FGF。尽管在这一领域取得了很大进展，但临床试验的结果令人失望，需要更安全、更有效的方法。为此，用于治疗性新血管形成的生物制剂必须在目前研究充分的类别之外进行探索。本文综述了利用小分子药物诱导和促进新生血管形成的新途径。具体而言，四类新的和现有的分子进行了讨论，包括转录激活剂，受体选择性激动剂和拮抗剂，天然产物衍生的小分子，和新的合成小分子。
Vascular growth and remodeling are complex processes that depend on the proper spatial and temporal regulation of many different signaling molecules to form functional vascular networks. The ability to understand and regulate these signals is an important clinical need with the potential to treat a wide variety of disease pathologies. Current approaches have focused largely on the delivery of proteins to promote neovascularization of ischemic tissues, most notably VEGF and FGF. Although great progress has been made in this area, results from clinical trials are disappointing and safer and more effective approaches are required. To this end, biological agents used for therapeutic neovascularization must be explored beyond the current well-investigated classes. This review focuses on potential pathways for novel drug discovery, utilizing small molecule approaches to induce and enhance neovascularization. Specifically, four classes of new and existing molecules are discussed, including transcriptional activators, receptor selective agonists and antagonists, natural product-derived small molecules, and novel synthetic small molecules.