CSF1R-IN-3 is a potent, selective and orally bioavailable CSF-1R inhibitor with IC50 of 2.1 nM. CSF1R-IN-3 concentration-dependently inhibited the phosphorylation of CSF-1R and AKT in both BMDMs and PMA-differentiated THP-1 cells. CSF1R-IN-3 shows high binding affinity to CSF-1R with a dissociation constant (KD) of 3.4 nM in SPR assays. CSF1R-IN-3 (30 and 100 nM) potently inhibits the migration of macrophages. CSF1R-IN-3 (30 and 100 nM) could downregulate the messenger RNA (mRNA) expressions of Il10, Arg1, Chil3, Retnla, and Vegf and upregulate the expressions of Il12, Tnf, Il6, and Nos2. CSF1R-IN-3 inhibits the progression of colorectal cancer by suppressing the migration of macrophages, reprograming M2-like macrophages to the M1 phenotype, and enhancing the antitumor immunity.
