Gilteritinib (ASP2215)

Name: Gilteritinib (ASP2215)
Brand: Selleck Chemicals
SKU: S7754
Rating: 5 (8 reviews)

For research use only.

Catalog No.S7754

8 publications

Gilteritinib (ASP2215) Chemical Structure

CAS No. 1254053-43-4

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).

Selleck's Gilteritinib (ASP2215) has been cited by 8 publications

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Biological Activity

Description

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].

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MV4-11 cells	NULxTYVJS2WubDDjfYNt\SCjc4PhfS=>	MVGxMEA{NCBzMDygZY5lKDNyIH7N	MkP3NlQhcA>?	M3jhdnRp\SCvZXHuJJBzd3CxcoTpc44hd2ZiTW[0MVEyKGOnbHzzJIlvKEdzIIDoZZNmKHencnWgd4lodmmoaXPhcpRtgSCrbnPy[YF{\WRiYYSg[4ltfGW{aYTpcoljKGOxbnPlcpRz[XSrb37zJI9nKDNiKE[5MlAmQyCSPECuNFEqKGGwZDCxNEBvVSBqN{CuO{U8KFB:MD6wNFEqNg>?	Mm\SN\|ExPjlyMUW=
MOLM-13 cells	M{[0b2Fxd3C2b4Ppd{Bie3OjeR?=	MnG2NUwhOyxiMUCsJFMxNCCjbnSgNVAxKG6P	NUPhXnlDPDhiaB?=	NHHYV3B{cWewaX\pZ4FvfCCrbnPy[YF{\XNiaX6geIhmKHCncnPlcpRi\2Vib3[gZY5v\XirbjDWMZBwe2m2aY\lJINmdGy\|IHH0JINwdmOnboTyZZRqd26\|IH;mJFMxKG6PIDizNk4xLSliYX7kJFExOCCwTTCoOVIvPCVrII\ldpN2eyClb370do9tKCh2LkGlLS=>	Mn\aN\|ExPjlyMUW=
32D/TKD cells	MnXMSpVv[3Srb36gZZN{[Xl?	NET4VYQ2OCCwTdMg	NFfifWg3KGh?	NYXtb3FTUW6qaXLpeI9vKG:oIITo[UBxcG:\|cHjvdplt[XSrb36gc4YhSWu2IH;uJHQ{ODh?	MmXMNlk2ODd4NkC=
TF-1 cells	MnH1SpVv[3Srb36gZZN{[Xl?	M2rhRlAtKDJyLDC4NEwhOjByIHHu[EA2ODBibl2=	MXOxJIg>	NHzIfWhocWy2ZYLpeIlvcWJiaHHzJIFvKEmFNUCgZYdicW6\|dDD3bYxlNXS7cHWgZ{1McXRib3[gNVAzKG6P	NHrvTWwzPzlyOEi4NS=>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-STAT5 / STAT5 / p-AKT / AKT / p-ERK / ERK; PubMed: 28516360 Invest New Drugs Immunoblot for phosphorylated AKT, ERK, and STAT5 in gilteritinib-treated MV4–11 cells. Blots from one study, which was done in triplicate, are shown. p-c-kit / c-kit; PubMed: 27908881 Blood TF-1 cells were treated with increasing concentrations gilteritinib in RPMI/10% FBS for 1 hour. Immunoprecipitation and immunoblotting were performed to detect the phosphorylation status of c-Kit and total c-Kit. p-FLT3(Y591) / FLT3; PubMed: 30344940 Oncotarget Cells were treated with or without 10 nM gilteritinib, or midostaurin for 6 h, and immunoblotting was performed using the indicated antibodies.	28516360 27908881 30344940

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

Cell Research: ^[1]	- Collapse 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. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: MV4-11 xenografted mice (Nude mice) Dosages: 1 mg/kg, 6 mg/kg, and 10 mg/kg Administration: oral (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	100 mg/mL (180.92 mM)
	Water	Insoluble
	Ethanol	'85 mg/mL

* 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.

Chemical Information Download Gilteritinib (ASP2215) SDF

Molecular Weight	552.71
Formula	C₂₉H₄₄N₈O₃
CAS No.	1254053-43-4
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC(=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)OC)NC5CCOCC5

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04140487	Recruiting	Drug: Azacitidine\|Drug: Gilteritinib\|Drug: Venetoclax	Recurrent Acute Myeloid Leukemia\|Recurrent Myelodysplastic Syndrome\|Refractory Acute Myeloid Leukemia\|Refractory Myelodysplastic Syndrome	M.D. Anderson Cancer Center\|National Cancer Institute (NCI)	December 17 2019	Phase 1\|Phase 2
NCT03730012	Recruiting	Drug: gilteritinib\|Drug: atezolizumab	Acute Myeloid Leukemia (AML)\|Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	June 19 2019	Phase 1\|Phase 2
NCT03964038	Completed	Drug: gilteritinib\|Drug: gilteritinib mini tablet	Healthy Volunteer	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	May 21 2019	Phase 1
NCT03625505	Recruiting	Drug: Venetoclax\|Drug: Gilteritinib	Acute Myeloid Leukemia (AML)	AbbVie\|Astellas Pharma Inc Genentech Inc.	October 18 2018	Phase 1

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FLT3 Signaling Pathway Map

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Gilteritinib (ASP2215)