Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro
Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro
复制标题
细胞周期蛋白依赖性激酶小分子抑制剂的体外抗血管生成潜力
DOI：
10.1007/s10456-010-9181-1
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发表时间：
2010
期刊：
影响因子：
9.8
通讯作者：
Vollmar AM
中科院分区：
文献类型：
--
作者：
Zahler S;Liebl J;Fürst R;Vollmar AM
小分子激酶抑制剂是有前途的新型药物。最初，它们是为了尽可能高的特异性而设计的。最近，这一概念受到了临床上更有效的多激酶抑制剂的挑战。这种范式的改变要求在不同的功能背景下重新检查已知的化合物。我们比较了 6 种报道的结构不同的细胞周期蛋白依赖性激酶 (Cdks) 抑制剂，了解它们对内皮细胞的功能影响（增殖、细胞周期、凋亡、迁移、管形成），以及它们对某些激酶（AKT、p38、ERK1/2、c-src、GSK3β）的作用。其中只有一些化合物在浓度高达 10 μM 时具有抗血管生成作用（氨基嘌呤醇、靛玉红-3'-单肟和 alsterpaullon），具体取决于它们的激酶谱。有趣的是，与其他机制相比，这些化合物对 Cdks 的影响似乎不太重要。 Aminopurvalanol、indirubin-3'-monoxime 和 alsterpaulone 可能会成为开发新型抗血管生成药物的有趣支架。
Small molecular kinase inhibitors are promising novel drugs. Initially, they were designed for the highest possible specificity. Recently, this concept has been challenged by multikinase inhibitors, which are clinically more potent. This change of paradigm calls for re-examination of already known compounds in different functional contexts. We have compared 6 reported structurally different inhibitors of cyclin-dependent kinases (Cdks) regarding their functional effects on endothelial cells (proliferation, cell cycle, apoptosis, migration, tube formation), as well as their actions on some kinases (AKT, p38, ERK1/2, c-src, GSK3β). Only some of these compounds had anti-angiogenic effects in concentrations up to 10 μM (aminopurvalanol, indirubin-3′-monoxime, and alsterpaullone), depending on their kinase profile. Interestingly, the impact of the compounds on Cdks seemed to be of minor importance, as compared to other mechanisms. Aminopurvalanol, indirubin-3′-monoxime, and alsterpaullone might turn out as interesting scaffolds for the development of novel anti-angiogenic drugs.
影响因子：
11.2
作者：
Tran, T. Cameron;Sneed, Blossom;Sandberg, Eric M.
通讯作者：
Sandberg, Eric M.
Paullones 的细胞内靶标
影响因子：
4.8
作者：
M. Knockaert;K. Wieking;S. Schmitt;M. Leost;K. Grant;J. Mottram;C. Kunick;L. Meijer
通讯作者：
L. Meijer