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Trk Inhibitor III, GNF-5837
(Z)-1-(3-((3-((1H-Pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)-4-methylphenyl)-3-(2-fluoro-5-(trifluoromethyl)phenyl)urea
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 µM) and Ba/F3-Tel-KDR and wt-Ba/F3 cells (IC50 = 3.0 and 5.6 µM). Displays ~100-fold greater selectivity among a panel of 59 closely related kinases and in 33 cellular kinase assays. Weakly active against relevant cytochrome P450 isozymes and hERG channel, and exhibit adequate microsomal stability, pharmacokinetic profile and efficacy in mice and rats. Suppresses tumor growth in a mouse RIE-TrkAmNGF xenograft model (50 mg/kg, p.o.).
产品信息
Form Orange powder
Molar mass 535.5
Protect from Light 是的
Packaged under inert gas 是的
Purity ≥98% by HPLC
Solubility DMSO
Chemical formula C28H21F4N5O2
CAS number 1033769-28-6
商店和运输信息
Storage +2°C to +8°C
Ship Ambient Temperature Only
Standard Handling |