Name: Gilteritinib (ASP2215)
Brand: Selleck Chemicals
SKU: S7754
Rating: 5 (38 reviews)

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).

Gilteritinib (ASP2215) Chemical Structure

CAS: 1254053-43-4

Selleck's Gilteritinib (ASP2215) has been cited by 38 publications

Purity & Quality Control

Products often used together with Gilteritinib (ASP2215)

Quizartinib (AC220)

Gilteritinib exhibits a stronger proapoptotic effect in hypoxia and coculture with bone marrow stromal cells than Quizartinib.

Dumas PY, et al. Clin Cancer Res. 2021 Nov 1;27(21):6012-6025.

FF-10101

FF-10101 induces significantly more apoptosis of MOLM-14 cells in HS5-conditioned media compared to gilteritinib.

Ferng TT, et al. Mol Cancer Ther. 2022 May 4;21(5):844-854.

Venetoclax (ABT-199)

Gilteritinib and Venetoclax combination gives a highly modified composite complete response rate and FLT3 molecular response rates.

Daver N, et al. J Clin Oncol. 2022 Dec 10; 40(35): 4048–4059.

Fimepinostat (CUDC-907)

Gilteritinib and Fimepinostat, in combination, gives synergistic antileukemic activity against FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) cell lines MOLM-13/MV4-11.

Qiao X, et al. Blood Cancer J. 2021 Jun 7;11(6):111.

Midostaurin

Gilteritinib and Fimepinostat combination with venetoclax potently and synergistically induces apoptosis in FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) cell lines MOLM-13/MV4–1.

Ma J, et al. Clin Cancer Res. 2019 Nov 15;25(22):6815-6826.

Gilteritinib (ASP2215) Related Products

Related Targets	FLT3-WT FLT3-ITD FLT3-D835Y	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	Click to Expand

Signaling Pathway

FLT3 Signaling Pathway

Choose Selective FLT3 Inhibitors

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MV4-11 cells	Cell cycle assay	1, 3, 10, and 30 nM	24 h	The mean proportion of MV4-11 cells in G1 phase were significantly increased at gilteritinib concentrations of 3 (69.0%; P<0.01) and 10 nM (70.7%; P<0.001).	31069015
MOLM-13 cells	Apoptosis assay	1, 3, 10, 30, and 100 nM	48 h	significant increases in the percentage of annexin V-positive cells at concentrations of 30 nM (32.0%) and 100 nM (52.4%) versus control (4.1%)	31069015
32D/TKD cells	Function assay	50 nM	6 h	Inhibiton of the phosphorylation of Akt on T308	29507660
TF-1 cells	Function assay	0, 20, 80, 200 and 500 nM	1 h	gilteritinib has an IC50 against wild-type c-Kit of 102 nM	27908881
BA/F3	Function assay			Inhibition Assay: A recombinant retrovirus was created from expression plasmid FLAG-EML4-ALKv1/pMX-iresCD8 in which cDNA for EMLA-ALK fusion protein v1 was integrated, and injected into mouse lymphoid cell line BA/F3 cells. Using a magnetic bead reagent f, IC50 = 0.0015 μM.	ChEMBL
BA/F3	Function assay			Inhibition Assay: A recombinant retrovirus was created from expression plasmid FLAG-EML4-ALKv1/pMX-iresCD8 in which cDNA for EMLA-ALK fusion protein v1 was integrated, and injected into mouse lymphoid cell line BA/F3 cells. Using a magnetic bead reagent f, IC50 = 0.0015 μM.	ChEMBL
Vero	Antiviral assay		24 hr	Antiviral activity against SARS-CoV-2 (viral titer) measured by plaque assay in Vero cells at MOI 0.0125 after 24 hr, IC50 = 6.76 μM.	ChEMBL
Vero	Cell viability assay		72 hr	Cell viability measured by CellTiter-Glo assay in Vero cells at MOI 0.05 after 72hr, CC50 = 37.16 μM.	ChEMBL
Click to View More Cell Line Experimental Data

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
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].
Cell Research	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
Experimental Result Images	Western blot	p-STAT5 / STAT5 / p-AKT / AKT / p-ERK / ERK p-c-kit / c-kit p-FLT3(Y591) / FLT3		28516360

In Vivo
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].
Animal Research	Animal Models	MV4-11 xenografted mice (Nude mice)
	Dosages	1 mg/kg, 6 mg/kg, and 10 mg/kg
	Administration	oral

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06022003	Not yet recruiting	AML Adult\|Refractory AML\|Relapsed Adult AML\|FLT3-TKD Mutation\|FLT3-ITD	French Innovative Leukemia Organisation\|Acute Leukemia French Association	December 15 2023	Phase 2
NCT05520567	Recruiting	Acute Myeloid Leukemia (AML)\|FLT3-mutated Acute Myeloid Leukemia	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	January 27 2023	Phase 1\|Phase 2
NCT05791890	Active not recruiting	Acute Myeloid Leukemia	University of Rome Tor Vergata	May 31 2022	--

References

Chemical Information & Solubility

Molecular Weight	552.71	Formula	C₂₉H₄₄N₈O₃
CAS No.	1254053-43-4	SDF	Download Gilteritinib (ASP2215) SDF
Smiles	CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC(=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)OC)NC5CCOCC5
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 4 mg/mL ( (7.23 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.					In vivo Formulation Calculator
	Clear solution	5%DMSO 1 Corn oil	1.0mg/ml (1.81mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.	In vivo Formulation Calculator
Clear solution	5%DMSO 1 Corn oil	0.2mg/ml (0.36mM)	Taking the 1 mL working solution as an example, add 50 μL of 4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 Corn oil	0.25mg/ml (0.45mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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