GNF-5837

1033769-28-6

C28H21F4N5O2

DMSO : >= 32 mg/mL (59.76 mM); H2O : < 0.1 mg/mL (insoluble)

Protein Tyrosine Kinase/RTK; Neuronal Signaling

GNF-5837 is a potent pan-Trk inhibitor which display antiproliferative effects in cellular Ba/F3 assays (IC50 values are 7, 9 and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively). IC50 Value: 7/9/11 nM (Tel-TrkC/Tel-TrkB/Tel-TrkA) [1] Target: pan-Trk GNF-5837 is an orally bioavailable oxindole compound that and acts as a potent, reversible and type II DFG-out inhibitor of pan-Trk activity (IC50 = 8 and 12 nM for TrkA and TrkB). Shown to target Trk (tropomyosin receptor kinase) ATP binding cleft and an immediately adjacent hydrophobic pocket. Preferentially arrests the proliferation of Ba/F3 cells fused with Tel-TrkA, Tel-TrkB and Tel-TrkC (IC50 = 11, 9 and 7 nM, respectively) and in Ba/F3 and RIE cells expressing both TrkA and NGF (IC50 = 42 and 17 nM, respectively) over Mo7e-c-Kit and Rat-A10-PDGFR (IC50 = 1 and 0.5 uM) and Ba/F3-Tel-KDR and wt-Ba/F3 cells (IC50 = 3.0 and 5.6 uM). GNF-5837 displays ca.100-fold greater selectivity among a panel of 59 closely related kinases and in 33 cellular kinase assays. GNF-5837 weakly antagonize relevant cytochrome P450 isozymes and hERG channel, and exhibit adequate microsomal stability, pharmacokinetic profile and efficacy in mice and rats. GNF-5837 suppresses tumor growth in a mouse RIE-TrkAmNGF xenograft model (50 mg/kg, p.o.) [1].