Teillet Florence, Boumendjel Ahcene, Boutonnat Jean, Ronot Xavier
Laboratoire de Dynamique Cellulaire, EPHE, Laboratoire TIMC-IMAG, UMR-CNRS 5525, Université Joseph Fourier, Pavillon Taillefer, 38706 La Tronche Cedex, France.
Med Res Rev. 2008 Sep;28(5):715-45. doi: 10.1002/med.20122.
Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed.
酪氨酸激酶受体（RTKs）在细胞分裂周期的调控中起着关键作用。目前已描述了50多种分为几个亚家族的RTKs。对这些酶的抑制已成为一个重要的研究领域。能够抑制这些酶活性的化合物有望表现出抗增殖特性。黄酮类化合物是作为RTK抑制剂的各种小分子的代表。这些天然存在的化合物能够与几种激酶的ATP结合位点结合。目前最合理的解释这些物质对激酶作用的假说是，黄酮类化合物的色原酮部分充当受体辅助因子ATP的腺嘌呤部分的模拟物。在这篇综述中，我们报告了黄酮类天然和合成衍生物作为RTK抑制剂活性的最新研究结果。讨论了其作用机制、治疗用途和潜在的临床应用。
