| Name | Gilteritinib hemifumarate |
| Description | Gilteritinib hemifumarate (ASP2215 hemifumarate) is a potent ATP-competitive dual FLT3 (IC50: 0.29 nM) and AXL (IC50: 0.73 nM) inhibitor for the treatment of relapsed or refractory FLT3 mutant AML. |
| In vitro | Gilteritinib (ASP2215) inhibits FLT3, leukocyte tyrosine kinase (LTK), anaplastic lymphoma kinase (ALK), and AXL kinases by over 50% at 1 nM, with an IC50 value of 0.29 nM for FLT3. It is approximately 800-fold more potent for FLT3 inhibition than for c-KIT[1].
In addition, Gilteritinib inhibits the activity of eight out of 78 tested kinases by over 50% at concentrations of either 1 nM (FLT3, LTK, ALK, and AXL) or 5 nM (TRKA, ROS, RET, and MER). The IC50s are 0.29 nM for FLT3 and 0.73 nM for AXL. The antiproliferative activity of Gilteritinib is evaluated against MV4-11 and MOLM-13 cells, which endogenously express FLT3-ITD. After 5 days of treatment, Gilteritinib inhibits the growth of MV4-11 and MOLM-13 cells with mean IC50s of 0.92 nM (95% CI: 0.23-3.6 nM) and 2.9 nM (95% CI: 1.4-5.8 nM), respectively.
Growth suppression of MV4-11 cells is accompanied by the inhibition of FLT3 phosphorylation. Relative to vehicle control cells, phosphorylated FLT3 levels are 57%, 8%, and 1% after 2 h of treatment with 0.1 nM, 1 nM, and 10 nM Gilteritinib, respectively. Additionally, doses as low as 0.1 nM or 1 nM result in the suppression of phosphorylated ERK, STAT5, and AKT, all downstream targets of FLT3 activation.
To investigate the effects of Gilteritinib on AXL inhibition, MV4-11 cells expressing exogenous AXL are treated with Gilteritinib. At concentrations of 1 nM, 10 nM, and 100 nM for 4 h, Gilteritinib treatment decreases phosphorylated AXL levels by 38%, 29%, and 22%, respectively[2]. |
| In vivo | With oral administration of Gilteritinib (ASP2215) at 10 mg/kg for 4 days in MV4-11 xenografted mice, the concentration of Gilteritinib in tumors is more than 20-fold higher than that in plasma. Treatment with Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth, inducing complete tumor regression at doses higher than 6 mg/kg. Additionally, Gilteritinib decreases tumor burden in the bone marrow and prolongs the survival of mice intravenously transplanted with MV4-11 cells[1]. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 3 mg/mL (4.91 mM), Sonication is recommended.
H2O : 1 mg/mL (1.64 mM), Sonication is recommended.
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| Keywords | TAMReceptor | TAM Receptor | Gilteritinib Hemifumarate | Gilteritinib | FLT3 | AXL | ASP-2215 Hemifumarate | ASP2215 Hemifumarate | ASP-2215 | ASP2215 | ASP 2215 Hemifumarate | ASP 2215 |
| Inhibitors Related | Bemcentinib | Gilteritinib | Sunitinib | Fostamatinib | Nintedanib | Ripretinib | Sorafenib | Pexidartinib | Tepotinib | Brigatinib | Cabozantinib S-malate | Onatasertib |
| Related Compound Libraries | Failed Clinical Trials Compound Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | EMA Approved Drug Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Inhibitor Library | Anti-Cancer Approved Drug Library | FDA-Approved Kinase Inhibitor Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
