FGFR1 inhibitor-11 (compound 5g) effectively targets and binds to FGFR1, subsequently inhibiting the downstream signaling pathways ERK1/2 and IκBα/NF-κB, which results in the suppression of RANKL-induced osteoclastogenesis. This compound also exhibits oral bioactivity [1].

FGFR1 inhibitor-11 (compound 5g): In a Cell Viability Assay with BMDMs, at concentrations of 0, 1.25 μM, 2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM, 80 μM, and 160 μM, and an incubation time of 48 hours, it exhibited toxicity above 40 μM. In Immunofluorescence with osteoclasts, at concentrations of 0, 2.5 μM, 5 μM, and 10 μM, it significantly and dose-dependently increased the protein level of F-actin. In Real Time qPCR with BMDMs at a 10 μM concentration over 1, 2, and 3 days, it inhibited the mRNA expression levels of the primary osteoclast-specific marker genes (Ctsk, Mmmp9, and others).

FGFR1 inhibitor-11 (15-30 mg/kg; oral administration; twice daily) significantly prevents bone loss (BV, T-BMD, etc.) in mice [1].