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].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

unphosphorylated FGFR1:0.84 μM (IC50)

unphosphorylated FGFR2:1.23 μM (IC50)

FGFR1 autophosphorylation:2.8 μM (IC50)

FGFR2 autophosphorylation:1.9 μM (IC50)

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]. Western Blot Analysis[1] Cell Line: Kato III human gastric carcinoma cells Concentration: 3.8, 7.5, 15, 30, 60 μM Incubation Time: For 2 hours Result: Reduced the degree of phosphorylation of FGFR (predominantly FGFR2) in a concentration-dependent manner, without decreasing β-actin.

[1]. Eathiraj S, et al. A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J Biol Chem. 2011 Jun 10;286(23):20677-87.