New Insight into the Anti-liver Fibrosis Effect of Multitargeted Tyrosine Kinase Inhibitors: From Molecular Target to Clinical Trials.
New Insight into the Anti-liver Fibrosis Effect of Multitargeted Tyrosine Kinase Inhibitors: From Molecular Target to Clinical Trials.
复制标题
多靶点酪氨酸激酶抑制剂抗肝纤维化作用的新见解：从分子靶点到临床试验。
DOI：
10.3389/fphar.2015.00300
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发表时间：
2015
影响因子：
5.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Qu K;Huang Z;Lin T;Liu S;Chang H;Yan Z;Zhang H;Liu C
酪氨酸激酶 (TK) 是酪氨酸蛋白激酶家族，在调节多种生理细胞过程中具有重要功能。 TK 过度活跃会扰乱细胞稳态，并与某些疾病（包括各种纤维化疾病）的发生有关。在肝纤维化方面，血管内皮生长因子受体、血小板源性生长因子受体、成纤维细胞生长因子受体和表皮生长因子受体激酶等多种TK已被确定为胶原蛋白生成的中心介质和抗肝纤维化治疗的潜在靶点。鉴于 TK 在肝纤维化过程中的重要作用，异常 TK 活性的多靶点抑制剂，包括索拉非尼、厄洛替尼、伊马替尼、舒尼替尼、尼洛替尼、布立尼布和瓦他拉尼，已被证明具有治疗肝纤维化的潜力。该领域的研究人员在临床前动物模型和肝纤维化患者中观察到使用这些多靶点 TK 抑制剂的有益效果。本文将简要总结多靶点TK抑制剂的抗肝纤维化作用及分子机制。
Tyrosine kinases (TKs) is a family of tyrosine protein kinases with important functions in the regulation of a broad variety of physiological cell processes. Overactivity of TK disturbs cellular homeostasis and has been linked to the development of certain diseases, including various fibrotic diseases. In regard to liver fibrosis, several TKs, such as vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor, and epidermal growth factor receptor kinases, have been identified as central mediators in collagen production and potential targets for anti-liver fibrosis therapies. Given the essential role of TKs during liver fibrogenesis, multitargeted inhibitors of aberrant TK activity, including sorafenib, erlotinib, imatinib, sunitinib, nilotinib, brivanib and vatalanib, have been shown to have potential for treating liver fibrosis. Beneficial effects are observed by researchers of this field using these multitargeted TK inhibitors in preclinical animal models and in patients with liver fibrosis. The present review will briefly summarize the anti-liver fibrosis effects of multitargeted TK inhibitors and molecular mechanisms.