The Walter and Eliza Hall Institute of Medical Research, 4 Research Avenue, La Trobe R & D Park, Bundoora, VIC 3086, Australia.
Expert Opin Ther Pat. 2011 Feb;21(2):147-65. doi: 10.1517/13543776.2011.545348. Epub 2011 Jan 5.
Macrophages are key drivers of both the innate and adaptive immune systems. The cellular receptor for CSF-1 and IL-34, c-FMS, is a key component of the mechanism(s) by which macrophages are regulated. Several drug discovery programs aimed at uncovering inhibitors of the tyrosine kinase activity of this receptor are now entering clinical phase, and the prospect of readjusting the behavior of macrophages in a number of pathological situations, such as inflammation and cancer, is now on us.
In this review, we evaluate the available patent literature on the topic of small molecule inhibitors of c-FMS. By way of background, we review the biology of c-FMS and make an analysis of the therapeutic opportunities that a small molecule c-FMS inhibitor might present. In order to place the pharmacology in perspective, we examine the literature concerning the role of the CSF-1-IL-34-c-FMS axis in macrophage function as well as cell types related to macrophages, such as the osteoclast, the dendritic cell and microglia, and provide a background to the understanding of the therapeutic opportunities for c-FMS inhibitors as well as potential obstacles that could limit their use.
The c-FMS receptor is a hot target for the development of novel regulators of macrophage behavior. Some nice candidates have been developed by a number of groups, and their recent entry into clinical phase testing means that we are now on the cusp of a fuller understanding of the role of these important regulators of the innate and adaptive immune systems in the development of cancer and inflammatory diseases.
巨噬细胞是先天和适应性免疫系统的主要驱动因素。细胞因子 CSF-1 和 IL-34 的受体 c-FMS 是调节巨噬细胞的机制的关键组成部分。目前，有几个旨在发现该受体酪氨酸激酶活性抑制剂的药物发现计划正在进入临床阶段，现在我们有机会调整巨噬细胞在多种病理情况下（如炎症和癌症）的行为。
在这篇综述中，我们评估了关于小分子 c-FMS 抑制剂的现有专利文献。作为背景，我们回顾了 c-FMS 的生物学，并对小分子 c-FMS 抑制剂可能带来的治疗机会进行了分析。为了从药理学角度进行分析，我们研究了 CSF-1-IL-34-c-FMS 轴在巨噬细胞功能以及与巨噬细胞相关的细胞类型（如破骨细胞、树突状细胞和小胶质细胞）中的作用的文献，并为理解 c-FMS 抑制剂的治疗机会以及可能限制其应用的潜在障碍提供了背景。
c-FMS 受体是开发新型巨噬细胞行为调节剂的热门靶点。一些不错的候选药物已经被多个研究小组开发出来，并且它们最近进入了临床阶段测试，这意味着我们现在正处于更全面地理解这些先天和适应性免疫系统重要调节剂在癌症和炎症性疾病发展中的作用的边缘。
