Gilteritinib hemifumarate Chemical Properties

storage temp. 

Store at -20°C

solubility 

Water: 2 mg/mL (3.27 mM); DMSO: 1.74 mg/mL (2.85 mM and warming)

form 

Solid

color 

White to yellow

InChIKey

RXDWJNODTRVCER-WLHGVMLRSA-N

SMILES

C(/C(=O)O)=C\C(=O)O.N(C1C=CC(N2CCC(N3CCN(C)CC3)CC2)=C(OC)C=1)C1=NC(NC2CCOCC2)=C(CC)N=C1C(=O)N

Gilteritinib hemifumarate Usage And Synthesis

Uses

Gilteritinib (ASP2215) hemifumarate is a potent and ATP-competitive FLT3/AXL inhibitor with IC50 of 0.29 nM/0.73 nM, respectively.

Mechanism of action

Gilteritinib hemifumarate, also known as ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT3-D835 mutations. In invitro, among the 78 tyrosine kinases tested, ASP2215 inhibited FLT3, LTK, 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, the inhibition of which is linked to a potential risk of myelosuppression. ASP2215 inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM, accompanied with inhibition of pFLT3, pAKT, pSTAT5, pERK, and pS6. ASP2215 decreased tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells. ASP2215 may have potential use in treating AML.

in vivo

IC 50

Axl

References

[1] ASP2215, a novel FLT3/AXL inhibitor: Preclinical evaluation in acute myeloid leukemia (AML). 2014 ASCO Annual Meeting.
[2] Mori M, et al. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest New Drugs. 2017 Oct;35(5):556-565. DOI:10.1007/s10637-017-0470-z