Definition

An orally bioavailable inhibitor of colony stimulating factor 1 receptor (CSF1R; CSF-1R; CD115; M-CSFR), discoid domain receptor type 1 (DDR1) and vascular endothelial growth factor receptor type 2 (VEGFR2), with potential antineoplastic activity. Upon oral administration, CSF-1R/DDR1/VEGFR2 inhibitor C019199 targets, binds to and inhibits the activity of CSF-1R. This inhibits CSF1R activation and CSF1R-mediated signaling, thereby inhibiting the activities of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), and preventing immune suppression in the tumor microenvironment (TME). This enhances antitumor T-cell immune responses and inhibits the proliferation of tumor cells. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), is a cell-surface receptor that plays major roles in tumor cell proliferation and metastasis. C019199 also targets, binds to and inhibits the activity of DDR1 and VEGFR2. Blocking DDR1, a protein expressed on tumor cells that binds collagen to make a minimally permeable physical barrier that blocks immune cells in the TME from interacting with and attacking the tumor, causes the collagen fibers to lose alignment and loosen. This creates gaps in the tumor barrier, thereby allowing cytotoxic T-cells to enter and attack the tumor. Blocking VEGFR2 results in the inhibition of tumor angiogenesis and tumor cell proliferation.