ARQ 069

ARQ 069 (3.8-60 ?M; for 2 hours) reduces the degree of phosphorylation of FGFR (predominantly FGFR2) in a concentration-dependent manner, without decreasing ?-actin. ARQ 069 shows an affinity for FGFR2 of 5.2 ?M. ARQ 069 inhibits FGFR phosphorylation in Kato III cells (IC50: 9.7 ?M) . ARQ 069 targets the inactive forms of FGFR1 and FGFR2 kinases and inhibits their enzymatic activity. When ARQ 069 is preincubated with either phosphorylated FGFR1 or FGFR2, the potency of ARQ 069 in inhibiting Pyk2 phosphorylation is markedly reduced, with IC50 values determined to be greater than 30 and 24.8 ?M for FGFR1 and FGFR2, respectively. ARQ 069 exhibits at least a 20-fold preference for binding to the unphosphorylated, inactive forms of FGFR1 and FGFR2.