Definition

An orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) Axl (UFO), Mer, and colony stimulating factor-1 receptor (CSF1R; CSF-1R; CD115; M-CSFR), with potential immunomodulatory, chemo-sensitizing and antineoplastic activities. Upon oral administration, Axl/Mer/CSF1R inhibitor Q702 targets, binds to and blocks the activity of Axl, Mer and CSF1R, thereby blocking Axl-, Mer- and CSF1R-mediated signaling pathways. This inhibits proliferation of Axl- and Mer-expressing tumor cells. In addition, blocking Axl- and Mer-mediated signaling may re-activate the innate immune system against cancer cells. Blocking CSF1R-mediated signaling inhibits the activities of tumor-associated macrophages (TAMs), regulatory T cells (Tregs) and recruitment of myeloid-derived suppressor cells (MDSCs). Altogether, this abrogates immune suppression in the tumor microenvironment (TME), 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, metastasis, and cancer-associated immune suppression. Axl and Mer, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and the inactivation of innate immunity in cancer. Their expression is associated with drug resistance and poor prognosis.