DCC-3014 (Vimseltinib) is a potent, selective, orally active inhibitor of colony-stimulating factor 1 receptor (CSF1R/c-Fms), inhibits CSF1R (Colony-stimulating factor 1 receptor) phosphorylated juxtamembrane domain (JMD) with IC50 of 2.8 nM, 100-fold less potency against fully phosphorylated CSF1R (IC50=290 nM). Vimseltinib significantly inhibited CSF1-stimulated expression of cFOS mRNA for > 24 hours post dose after single doses of 3.75 to 30 mg/kg in mouse spleens. In a PC3 prostate cancer peritibial implant xenograft model in nude mice, mice were treated with vimseltinib at 10 mg/kg, administered either once or twice daily on days 0 through 32 (until the average vehicle primary tumor reached 1,000 mm3 in size). Both regimens led to statistically significant protection from bone degradation. Vimseltinib treatment led to a statistically significant 68% decrease in liver CD68+ macrophages when dosed at 15 mg/kg/day in rats. CD68+ macrophages were also reduced in the colon[1]. In addition, DCC-3014 combined with the anti-PDL1 inhibitor avelumab would be safe and tolerable, decrease immunosuppressive myeloid cells, and increase cytotoxic T cells[2].
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