Molecular Formula | C29H44N8O3 |
Molar Mass | 552.71 |
Density | 1.242±0.06 g/cm3(Predicted) |
Melting Point | >157°C (dec.) |
Boling Point | 696.9±55.0 °C(Predicted) |
Solubility | DMSO |
Appearance | solid |
Color | Off-white to pale pink |
pKa | 14.39±0.50(Predicted) |
Storage Condition | -20°C |
Stability | Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
In vitro study | In MV4-11 and MOLM-13, Ba/F3 cells expressing mutant FLT3, Gilteritinib has potent inhibitory activity against FLT3-ITD (internal tandem repeat) and FLT3-D835Y. Gilteritinib reduces the phosphorylation of FLT3 and its downstream targets in cell experiments and animal models. Of the 78 kinases tested, Gilteritinib inhibited 8 of them at a concentration of 1 nM or 5 nM (I. E., the degree of inhibition exceeded 50%). MV4-11 cells were treated with Gilteritinib for 48 hours to induce apoptosis. After 24 hours of treatment, Gilteritinib can also down-regulate the expression of anti-apoptotic proteins such as MCL-1, BCL2L10 and survivin. |
In vivo study | In vivo experiments, gilteritinib can be distributed at high levels in xenograft tumor tissue after oral administration. In the FLT3-driven AML model, enrichment of gilteritinib in tumor tissue reduced FLT3 activity, tumor regression, and improved survival. The antitumor activity of gilteritinib correlates with its dual inhibition of phosphorylated FLT3 and phosphorylated STAT5. In addition, in the mouse IBMT model, gilteritinib reduces leukemia burden and prolongs survival. Treatment with gilteritinib has no apparent toxic effect in the mouse model. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.809 ml | 9.046 ml | 18.093 ml |
5 mM | 0.362 ml | 1.809 ml | 3.619 ml |
10 mM | 0.181 ml | 0.905 ml | 1.809 ml |
5 mM | 0.036 ml | 0.181 ml | 0.362 ml |