Flt-3 Inhibitor II

UsesA cell-permeable symmetrical indolylmethanone kinase inhibitor that is more selective toward Flt3 over PDGFR either in cell-based receptor autophosphorylation (IC50 = 40 nM vs. 300 nM) or in cell-free kinase reactions (IC50 = 33 nM vs. 171 nM) and potently induces apoptosis in Flt3-expressing primary AML patient blasts. Affects Abl- or Kit-dependent cell growth only at much higher concentrations (IC50 = 4.2 and ≥0.5 µM, respectively), while exhibiting little effect against IL-3-mediated cellular signaling. The molecular mechanism of inhibition is presumably due to interaction at the enzyme′s ATP-binding site.

General DescriptionA cell-permeable symmetrical indolylmethanone kinase inhibitor that is more selective toward Flt3 over PDGFR either in cell-based receptor autophosphorylation (IC50 = 40 nM vs. 300 nM) or in cell-free kinase reactions (IC50 = 33 nM vs. 171 nM) and potently induces apoptosis in Flt3-expressing primary AML patient blasts. Affects Abl- or Kit-dependent cell growth only at much higher concentrations (IC50 = 4.2 and ≥0.5 μM, respectively), while exhibiting little effect against IL-3-mediated cellular signaling. The molecular mechanism of inhibition is presumably due to interaction at the enzyme′s ATP-binding site.