For research use only. Not Intended for Therapeutic Use!
|Molecular Formula:||C₂₀H₂₀N₄O. HCl|
|IC50:||6.6 nM |
|We would like to match the lowest price on market if possible.|
KW-2449 is a multiple-targeted inhibitor, mostly for Flt3 with IC50 of 6.6 nM, modestly potent to FGFR1, Bcr-Abl and Aurora A; little effect on PDGFRβ, IGF-1R, EGFR.
IC50 value: 6.6 nM 
in vitro: Phosphorylation levels of FLT3 and STAT5 are decreased by KW-2449 in a dose-dependent manner. In addition, it potently inhibits ABL-T315I, which is associated with IM resistance, with IC50 of 4 nM. On the other hand, KW-2449 has little effect on PDGFRβ, IGF-1R, EGFR, and various serine/threonine kinases even at a concentration of 1 μM. KW-2449 has the potent growth inhibitory activities against not only FLT3/ITD-expressing leukemia cells but also FLT3/KDM-activated and wild-type FLT3-overexpressing leukemia cells . KW-2449 is rapidly absorbed and converted to a major metabolite M1.Preclinical studies reveal that KW-2449 is converted by monoamine oxidase-B (MAO-B) and aldehyde oxidase into its major metabolite M1.KW-2449 mediates cytotoxicity thru inhibition of FLT3/ITD.KW-2449 is a direct inhibitor of FLT3 and induces inhibition of its downstream target STAT5 . KW2449 interacts synergistically with HDACIs to induce apoptosis in Ph+ CML cells in a time- and concentration-dependent manner. KW2449 synergistically enhances the lethality of vorinostat/SNDX275 in CML cells.KW-2449 regimens are active against additional IM-resistant Bcr/Abl+ leukemia cells. KW2449 moderately reduces phosphorylation of histone H3, an indicator of Aurora B activity, in nocodozole-treated K562 cells .
in vivo: In the MOLM-13 tumor xenograft model, oral administration of KW-2449 for 14 days shows a potent and significant antitumor effect in a dose-dependent manner .