GNF-5837 (GNF5837) is a potent, selective, and orally bioavailable pan-TRK inhibitor with IC50 values of 11/9/7 nM against TRKA/B/C, respectively.
GNF-5837 demonstrated potent antiproliferation activity with IC50 of 42 nM in Ba/F3 cells expressing TRKA and NGF, with no effect in parental Ba/F3 cells whose proliferation is dependent on IL-3.
GNF-5837 potently inhibited cell growth and proliferation of RIE cells expressing TRKA and NGF with IC50 of 17 nM.
GNF-5837 showed significant selectivity window for TRK over c-Kit and PDGFR in cellular assays (IC50>0.5 uM).
GNF-5837 (25-100mg, p.o.) demonstrated 72 and 100% tumor regression at 50 and 100 mg/kg in tumor xenografts derived from RIE cells expressing both TRKA and NGF.
