Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV, 3, I-16132, Genova, Italy.
Curr Med Chem. 2011;18(19):2921-42. doi: 10.2174/092986711796150531.
Fyn is a non-receptor tyrosine kinase belonging to the Src family kinases. It has been shown to play important roles in neuronal functions, including myelination and oligodendrocytes formation, and in inflammatory processes. It has also demonstrated its involvement in signaling pathways that lead to severe brain pathologies, such as Alzheimer's and Parkinson's diseases. Moreover, Fyn is upregulated in some malignancies. Experimental studies demonstrated that Fyn inhibition could be useful in the disruption of metabolic processes involved in cancer neurodegenerative diseases. Unfortunately, no specific Fyn inhibitor has been discovered till today, active compounds on other members of Src family or on different tyrosine kinases have also been reported. However, multitargeted inhibitors might be endowed with therapeutic potential. Indeed, as increasingly reported, also a not completely selective inhibitor of a specific protein could be therapeutically useful, affecting a number of cell pathways involved especially in cancer development. In this review, we report some examples of small molecule tyrosine kinase inhibitors for which data on Fyn inhibition, both in enzymatic and in cell assays, have been reported, with the aim of giving information as starting point for the researchers working in this field.
Fyn 是一种非受体酪氨酸激酶,属于Src 家族激酶。已证实其在神经元功能中发挥重要作用,包括髓鞘形成和少突胶质细胞形成,以及在炎症过程中。它还表明其参与导致严重脑病理学的信号通路,如阿尔茨海默病和帕金森病。此外,Fyn 在一些恶性肿瘤中上调。实验研究表明,抑制 Fyn 可能有助于破坏涉及癌症神经退行性疾病的代谢过程。不幸的是,迄今为止尚未发现特异性 Fyn 抑制剂,也报道了针对 Src 家族其他成员或不同酪氨酸激酶的活性化合物。然而,多靶点抑制剂可能具有治疗潜力。事实上,正如越来越多的报道所表明的那样,即使是一种对特定蛋白质不完全选择性的抑制剂也可能具有治疗作用,影响涉及癌症发展的许多细胞途径。在这篇综述中,我们报告了一些小分子酪氨酸激酶抑制剂的例子,这些抑制剂在酶和细胞测定中均报告了对 Fyn 的抑制作用,旨在为该领域的研究人员提供信息作为起点。