Gilteritinib hemifumarate

SKU: orb1737521

Description

Gilteritinib hemifumarate (ASP2215 hemifumarate) is a highly potent, ATP-competitive dual inhibitor targeting FLT3 and AXL kinases, with IC50 values of 0.29 nM and 0.73 nM, respectively. It is a key research compound for studying relapsed or refractory FLT3-mutant acute myeloid leukemia (AML), utilized in both in vitro cellular assays and in vivo xenograft models to investigate therapeutic mechanisms and resistance.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1254053-84-3
• MW: 610.75
• Purity: 99.78%
• Formula: C₂₉H₄₄N₈O₃.1/2C₄H₄O₄
• SMILES: C(=C/C(O)=O)\C(O)=O.N(C=1C(C(N)=O)=NC(CC)=C(NC2CCOCC2)N1)C3=CC(OC)=C(C=C3)N4CCC(CC4)N5CCN(C)CC5
• Target: TAM Receptor,FLT
• Solubility: H2O:1 mg/mL (1.64 mM);DMSO:3 mg/mL (4.91 mM)

Bioactivity

• Target IC50:
  MOLM-13:2.9 nM|MV-4-11 cells:0.92 nM|FLT3:0.29 nM|Axl:0.73 n M
• 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.
• 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. 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Gilteritinib, Gilteritinib Hemifumarate, FLT3, AXL, ASP 2215, ASP 2215 Hemifumarate, ASP2215, ASP-2215, ASP2215 Hemifumarate, ASP2215 hemifumarate, ASP-2215 Hemifumarate, TAM Receptor, TAMReceptor

Compound Identifiers

PubChem CID

155520090