c-FMS inhibitors: a patent review

Introduction: 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. Areas covered: 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. Expert opinion: 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.