ABT-869 CAS NO.796967-16-3

linifanib (abt-869; al-39324) is a novel, potent atp-competitive vegfr/pdgfr inhibitor for kdr, csf-1r, flt-1/3 and pdgfrβ with ic50 of 4 nm, 3 nm, 3 nm/4 nm and 66 nm respectively.
ic50 value: 4 nm/3 nm/3 nm/4 nm /66 nm(kdr/csf-1r/flt-1/flt-3pdgfrβ) [1]
target: vegfr/pdgfr
in vitro: linifanib shows inhibitory to kit, pdgfrβ and flt4 with ic50 of 14 nm, 66 nm and 190 nm in kinases assay. linifanib also inhibits ligand-induced kdr, pdgfrβ, kit, and csf-1r phosphorylation with ic50 of 2 nm, 2 nm, 31 nm and 10 nm at cellular level and this cellular potency could be affected by serum protein. linifanib suppresses vegf-stimulated huaec proliferation with ic50 of 0.2 nm. while linifanib has weak activity against tumor cells which are not induced by vegf or pdgf, except for mv4-11 leukemia cells (with constitutively active form of flt3) with ic50 of 4 nm. linifanib could cause a decrease in s and g2-m phases with a corresponding increase in the sub-g0-g1 apoptotic population in mv4-11 cells [1]. linifanib binds to the atp-binding site of csf-1r with ki of 3 nm [2]. linifanib (10 nm) exhibits a reduced phosphorylation of akt at ser473 and decreased phosphorylation of gsk3βat ser9 in ba/f3 flt3 itd cell lines [3].
in vivo: linifanib (0.3 mg/kg) results in complete inhibition of kdr phosphorylation in lung tissue. linifanib also inhibits the edema response with ed50 of 0.5 mg/kg. linifanib (7.5 and 15 mg/kg, bid) significantly inhibits both bfgf- and vegf-induced angiogenesis in the cornea. linifanib inhibits tumor growth in flank xenograft models including ht1080, h526, mx-1 and dld-1 with ed75 from 4.5-12 mg/kg. linifanib also shows efficacy in a431 and mv4-11 xenografts at low dose levels. linifanib (12.5 mg/kg bid) reveals a decrease of microvasculure density in mda-231 xenograft. linifanib shows a cmax and auc24 hours with 0.4 μg/ml and 2.7 μghour/ml in ht1080 fibrosarcoma model [1].