PLX647

PLX647 is an orally active, highly specific dual FMS and KIT kinase inhibitor, with IC₅₀s of 28 and 16 nM, respectively. PLX647 shows selectivity for FMS and KIT over a panel of 400 kinases at a concentration of 1 μM except FLT3 and KDR (IC₅₀s=91 and 130 nM, respectively)^[1]. In Vitro: In vitro, PLX647 potently inhibits proliferation of BCR-FMS cells, with an IC₅₀ of 92 nM. A corresponding Ba/F3 cell line expressing BCR-KIT is also quite sensitive to PLX647, with an IC₅₀ of 180 nM. PLX647 also inhibits endogenous FMS and KIT, as demonstrated by inhibition of the ligand-dependent cell lines M-NFS-60 (IC₅₀=380 nM) and M-07e (IC₅₀=230 nM), which express FMS and KIT, respectively^[1].
PLX647 potently inhibits the growth of FLT3–ITD-expressing MV4-11 cells (IC₅₀=110 nM). PLX647 displayed minimal inhibition of the proliferation of Ba/F3 cells expressing BCR–KDR (IC₅₀=5 μM). PLX647 inhibits osteoclast differentiation with an IC₅₀ of 0.17 μM^[1]. In Vivo: PLX647 (40 mg/kg; p.o.; twice daily for 7 days) reduces macrophage accumulation in UUO kidney and blood monocytes^[1].
PLX647 (40 mg/kg; p.o.; male Swiss Webster mice) reduces LPS-induced TNF-α and IL-6 release^[1].
PLX647 (20-80 mg/kg; p.o.; daily or twice daily from 27-41 days) shows effects on collagen-induced arthritis^[1].
PLX647 (30 mg/kg) results in significant inhibition of TRAP5b immunostaining and bone osteolysis. PLX647 (30 mg/kg BID) is able to prevent bone damage by the tumor cells^[1].