ARQ 069

ARQ 069, an analog of ARQ 523, inhibits FGFR in an enantiospecific manner. ARQ 069 targets the unphosphorylated, inactive forms of FGFR1/FGFR2 kinases (IC₅₀s of 0.84 μM and 1.23 μM, respectively). ARQ 069 inhibits FGFR1/FGFR2 autophosphorylation (IC₅₀s of 2.8 and 1.9 μM, respectively) through a mechanism in a non-ATP competitive dependent manner^[1]. In Vitro: ARQ 069 (3.8-60 μM; for 2 hours) reduces the degree of phosphorylation of FGFR (predominantly FGFR2) in a concentration-dependent manner, without decreasing β-actin^[1].
ARQ 069 shows an affinity for FGFR2 of 5.2 μM^[1].
ARQ 069 inhibits FGFR phosphorylation in Kato III cells with an IC₅₀ of 9.7 μM^[1].
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 μM 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^[1].
ARQ 068 is the R-enantiomer, and ARQ 069 is the S-enantiomer^[1].