fgfr2/3-in-2

FGFR2 3-IN-2 (compound 10) is an orally active inhibitor targeting FGFR2 and FGFR3. It exhibits IC50 values of 3.7 nM for FGFR2 and 31.2 nM for FGFR3, with a pre-incubation time of 1 hour. FGFR2 3-IN-2 demonstrates selectivity over FGFR1 4 and other kinases, and does not cause diarrhea or increased serum phosphate in vivo. In the SNU-16 gastric cancer model, FGFR2 3-IN-2 can induce tumor stasis or regression.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

S49076 HCl (S-49076 Hydrochloride) is an effective inhibitor of MET, AXL MER, and FGFR1 2 3. S49076 HCl potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 HCl inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1 2 and AXL. In tumor xenograft models, a good pharmacokinetic pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 HCl was established and correlated well with impact on tumor growth.