Pexidartinib

An oral-active, BBB-penatrant, potent mutil-targeted RTK inhibitor of CSF-1R, Kit, and Flt3 with IC50 of 20 nM, 10 nM and 160 nM, respectively; inhibits the CSF1-dependent proliferation with IC50 of 0.44 uM, 0.22 uMand 0.1 uM in M-NFS-60, Bac1.2F5 and M-07e cells, respectively; significantly inhibits PTX-induced tumor infiltration in mice.Skin Cancer Phase 2 Clinical (In Vitro) :Pexidartinib (PLX-3397) is a potent, selective and ATP-competitive CSF1R (cFMS) and c-Kit inhibitor, shows 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases, such as FLT3, KDR (VEGFR2), LCK, FLT1 (VEGFR1) and NTRK3 (TRKC), with IC50s of 160, 350, 860, 880, and 890 nM, respectively. (In Vivo) :Pexidartinib (PLX3397; 0.25, 1 mg/kg, twice daily for 8 days) inhibits the proliferation of microglia and BrdU-positive cells in neonatal mice.Pexidartinib (1 mg/kg, twice daily for 8 day) shows no obvious effect on the cleaved caspase-3-positive cells in mice.Pexidartinib (50 mg/kg; p.o.; every second day for 3 weeks) reduces tissue macrophage levels without affecting glucose homeostasis in mice.