1. Protein Tyrosine Kinase/RTK
  2. FLT3
    TAM Receptor

Gilteritinib (Synonyms: ASP2215)

Cat. No.: HY-12432 Purity: 99.55%
Handling Instructions

Gilteritinib is a potent FLT3/AXL inhibitor with IC50 of 0.29 nM/0.73 nM, respectively.

For research use only. We do not sell to patients.

Gilteritinib Chemical Structure

Gilteritinib Chemical Structure

CAS No. : 1254053-43-4

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 122 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 100 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 150 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 350 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 550 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Other Forms of Gilteritinib:

    Gilteritinib purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    Gilteritinib purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Gilteritinib is a potent FLT3/AXL inhibitor with IC50 of 0.29 nM/0.73 nM, respectively.

    IC50 & Target

    IC50: 0.29 nM (FLT3)[1]
    IC50: 0.35 nM (LTK), 0.73 nM (AXL), 1.2 nM (EML4-ALK), 230 nM (c-KIT)[2]

    In Vitro

    Of the 78 tyrosine kinases tested, 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, approximately 800-fold more potent than for c-KIT[1]. Gilteritinib inhibits the activity of eight of the 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. Gilteritinib inhibits FLT3 at an IC50 that is approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM). 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 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. In addition, doses as low as 0.1 nM or 1 nM result in the suppression of phosphorylated ERK, STAT5, and AKT, all of which are downstream targets of FLT3 activation. To investigate the effects of Gilteritinib on AXL inhibition, MV4-11 cells that expressed 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

    In MV4-11 xenografted-mice, the concentration of Gilteritinib (ASP2215) in tumors is more than 20-fold higher than that in plasma with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg. Further, Gilteritinib decreases tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells[1].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.8093 mL 9.0463 mL 18.0927 mL
    5 mM 0.3619 mL 1.8093 mL 3.6185 mL
    10 mM 0.1809 mL 0.9046 mL 1.8093 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [2]

    The kinase inhibitory activity of Gilteritinib is tested against a panel of 78 tested kinases using ATP concentrations that are approximately equal to the Km value for each kinase in a TK-ELISA or off-chip mobility shift assay. Initially, two concentrations of Gilteritinib (1 nM and 5 nM) are tested to assess each compound’s inhibitory effect on TK activity. Further studies are then conducted using a dose range of Gilteritinib to determine IC50 values for kinases in which activity is inhibited by >50% with 1 nM Gilteritinib as well as for c-KIT. TK-ELISA and MSA assays are used to conduct IC50 studies for FLT3, LTK, AXL, and c-KIT; the HTRF KinEASE-TK assay is performed to assess the IC50 value of echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)[2].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    Gilteritinib is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

    The effect of Gilteritinib on MV4-11 and MOLM-13 cells is assessed using the CellTiter-Glo Luminescent Cell Viability Assay. Subsequent studies are conducted to examine the effect of Gilteritinib and Quizartinib on Ba/F3 cells expressing either FLT3-ITD, FLT3-D835Y, FLT3-ITD-D835Y, FLT3-ITD-F691 L, or FLT3-ITD-F691I. MV4-11 and MOLM-13 cells are treated with DMSO or increasing concentrations of Gilteritinib (0.01, 0.1, 1, 10, and 100 nM) for 5 days, and cell viability is measured using CellTiter-Glo[2].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    Antitumor activity is evaluated in nude mice transplanted with MV4-11 AML cells. The pharmacokinetics in xenografted mice is also investigated. MV4-11 xenografted-mice are treated with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg[1].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    552.71

    Formula

    C₂₉H₄₄N₈O₃

    CAS No.

    1254053-43-4

    SMILES

    NC(C1=NC(CC)=C(NC2CCOCC2)N=C1NC3=CC(OC)=C(N4CCC(N5CCN(C)CC5)CC4)C=C3)=O

    Storage

    4°C, stored under nitrogen

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product name

     

    Salutation

    Applicant name *

     

    Email address *

    Phone number *

     

    Organization name *

    Country or Region *

     

    Requested quantity *

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    Gilteritinib
    Cat. No.:
    HY-12432
    Quantity: