College of Pharmacy , University of Sharjah , Sharjah 27272 , United Arab Emirates.
Department of Medicinal Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura 35516 , Egypt.
J Med Chem. 2018 Jul 12;61(13):5450-5466. doi: 10.1021/acs.jmedchem.7b00873. Epub 2018 Jan 17.
Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.
集落刺激因子-1 受体（CSF-1R），也称为 FMS 激酶，当其配体 CSF-1 过度刺激时，在引发炎症、癌症和骨骼疾病方面发挥重要作用。CSF-1R 的刺激调节先天免疫以及巨噬细胞分化和存活。另一种配体白细胞介素-34（IL-34）最近被报道以不同的方式激活 CSF-1R 受体。已经综述了 CSF-1R 与小胶质细胞之间的关系。CSF-1 抗体和小分子 CSF-1R 激酶抑制剂现已在动物模型和人类中进行了测试。在本观点中，我们讨论了 CSF-1 和 IL-34 在产生癌症、骨骼疾病和炎症中的作用。我们还回顾了 2012 年至 2017 年报道的新发现和改进的小分子激酶抑制剂和单克隆抗体，它们对 CSF-1R 表现出很强的活性。
