Gilteritinib (ASP2215)

Catalog No.S7754 Batch:S775401

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Technical Data

Formula

C29H44N8O3
Molecular Weight 552.71 CAS No. 1254053-43-4
Solubility (25°C)* In vitro DMSO 5 mg/mL (9.04 mM)
Ethanol 5 mg/mL (9.04 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Gilteritinib (ASP2215) is a small-molecule FLT3/AXL inhibitor with IC50 values of 0.29 nM and 0.73 nM for FLT3 and AXL, respectively. It inhibits FLT3 at an IC50 value that was approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM).
Targets
FLT3 [1]
(Cell-free assay)		 Axl [1]
(Cell-free assay)
0.29 nM 0.73 nM
In vitro Gilteritinib demonstrates potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4-11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3. Gilteritinib decreases the phosphorylation levels of FLT3 and its downstream targets in both cellular and animal models. 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)[1]. Gilteritinib treatment for 48h results in an induction of apoptosis in MV4-11 cells as determined by an increase in annexin V-positive cells. Gilteritinib also decreases the expression of anti-apoptotic proteins such as MCL-1, BCL2L10, and survivin, which are reported to be important in chemotherapy sensitivity, following 24h treatment[2].
In vivo In vivo, gilteritinib is distributed at high levels in xenografted tumors after oral administration. The decreased FLT3 activity and high intratumor distribution of gilteritinib translates to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. This antitumor activity is associated with a durable inhibition of phospho-FLT3 and phospho-STAT5. Furthermore, treatment with gilteritinib decreases the leukemic burden and prolongs survival in a mouse IBMT model. No overt toxicity is seen in mouse models treated with gilteritinib[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    MV4-11 cells

  • Concentrations

    0.1 nM, 1 nM, and 10 nM

  • Incubation Time

    2 h

  • Method

    MV4-11 cells are treated with DMSO or increasing concentrations of gilteritinib for 2 hours. Immunoprecipitation and immunoblot for phosphorylated FLT3 and total FLT3 are performed.
Animal Study:

[1]
  • Animal Models

    MV4-11 xenografted mice (Nude mice)

  • Dosages

    1 mg/kg, 6 mg/kg, and 10 mg/kg

  • Administration

    oral

Selleck's Gilteritinib (ASP2215) has been cited by 41 publications

The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia [ Genes Chromosomes Cancer, 2024, 63(1):e23217] PubMed: 38087879
Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks [ Immunity, 2023, 56(8):1778-1793.e10] PubMed: 37463581
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] PubMed: 37726279
A combinatorial therapeutic approach to enhance FLT3-ITD AML treatment [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101286] PubMed: 37951217
Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML [ Cell Rep Med, 2023, 4(11):101290] PubMed: 37992684
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] PubMed: 37726279
Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia [ Oncogene, 2023, 42(16):1272-1281] PubMed: 36739363
The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors [ Cell Death Discov, 2023, 9(1):44] PubMed: 36739272
An In Vitro Model for Acute Myeloid Leukemia Relapse Using the SORE6 Reporter [ Int J Mol Sci, 2023, 25(1)496] PubMed: 38203669
The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases [ Res Sq, 2023, rs.3.rs-2570204] PubMed: 36865133

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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