Macrophage colony-stimulating factor 1 receptor [1.4.1] (CSF1R [1.4.1])

The Macrophage colony-stimulating factor 1 receptor (CSF1R) is a class III receptor tyrosine kinase essential for the development, survival, and function of mononuclear phagocytes, including macrophages, monocytes, and microglia [1.2.1, 1.4.1]. It is activated by the binding of its ligands, colony-stimulating factor 1 (CSF-1) and interleukin-34 (IL-34), which triggers receptor dimerization and autophosphorylation of cytoplasmic tyrosine residues [1.2.2, 1.3.1]. This activation initiates signaling cascades such as the PI3K/AKT and MAPK/ERK pathways, regulating processes like cell proliferation, differentiation, and migration [1.2.1, 1.4.3]. In oncology, CSF1R is a key target because it mediates the recruitment of tumor-associated macrophages (TAMs), which promote tumor growth, angiogenesis, and immunosuppression within the tumor microenvironment [1.1.1, 1.3.3]. Beyond cancer, CSF1R mutations are linked to neurodegenerative disorders like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), and its signaling is involved in inflammatory conditions such as chronic graft-versus-host disease [1.3.5, 1.4.4]. Therapeutic strategies include small-molecule tyrosine kinase inhibitors like pexidartinib and vimseltinib, as well as monoclonal antibodies like axatilimab, which have been approved for specific indications [1.3.1, 1.3.2]. However, clinical use is often limited by safety concerns, most notably severe hepatotoxicity and systemic effects like hair depigmentation [1.3.1, 1.3.4].

Other names

CSF-1R [1.4.1]M-CSFR [1.4.1]CD115 [1.4.1]FMS [1.4.1]C-FMS [1.4.1]FIM2 [1.4.1]HDLS [1.4.1]BANDDOS [1.4.1]

Tyrosine kinase inhibition of the intracellular domain by small molecules prevents ATP binding and autophosphorylation, while monoclonal antibodies block the extracellular domain to prevent ligand binding or receptor dimerization [1.1.1, 1.3.1, 1.3.4, 1.3.5].