FLT3-IN-14

FLT3-IN-14 is a potent FLT3 inhibitor with IC50s of 5.6 nM and 1.4 nM for FLT3-WT and FLT3-ITD. FLT3-IN-14 reduces the phosphorylation of FLT3 (Y591), induces cell cycle arrest at G1 phase and apoptosis. FLT3-IN-14 significantly reduces the tumor growth in an MV4-11 xenograft mouse model[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FLT3

IC50: 1.4 nM (FLT-ITD), 5.6 nM (FLT3-WT)[1]

FLT3-IN-14 (compound 9c) (0-10 μM; 24 hours) inhibits the proliferation of tested twelve haematological cell lines with IC50s of 0.011-1.582 μM[1]. FLT3-IN-14 (0-10 μM; 72 hours) exhibits low toxicity, with GI50 greater than 10 μM, in resting lymphocytes[1]. FLT3-IN-14 (1-50 nM; 24 and 48 hours) accumulates annexin-V positive cells in a concentration and time-dependent manner[1]. FLT3-IN-14 (25-100 nM; 24 and 48 hours) induces a significant G1 arrest in both cell lines[1]. FLT3-IN-14 (1-50 nM; 24 hours) induces the dephosphorylation of FLT3[1]. Cell Proliferation Assay Cell Line: MOLT-4 , HL-60, KG-1, KG-1a, MOLM-13, MV4-11, NOMO-1, OCI-AML2, PL-21, THP-1, K-562, KCL-22[1] Concentration: 0-10 μM Incubation Time: 24 hours Result: Inhibited the proliferation of these twelve haematological cell lines with IC50s of 0.011-1.582 μM. Cell Cytotoxicity Assay Cell Line: PBL[1] Concentration: 0-10 μM Incubation Time: 72 hours Result: Exhibited low toxicity, with GI50 greater than 10 μM, in resting lymphocytes. Apoptosis Analysis Cell Line: MV4-11[1] Concentration: 1, 10 and 50 nM Incubation Time: 24 and 48 hours Result: Accumulated annexin-V positive cells in a concentration and time-dependent manner. Cell Cycle Analysis Cell Line: MOLM-13 and MV-14[1] Concentration: 25, 50, 75 and 100 nM Incubation Time: 24 and 48 hours Result: Induced a significant G1 arrest in both cell lines. Western Blot Analysis Cell Line: MV-14[1] Concentration: 1, 10 and 50 nM Incubation Time: 24 hours Result: Induced the dephosphorylation of FLT3.

FLT3-IN-14 (1.0 and 3.0 mg/kg; IP; daily for 28 days) significantly reduces tumor growth in a dose-dependent manner without sign of toxicity[1]. Animal Model: NOD/SCID female mice (subcutaneously implanted MV4-11)[1] Dosage: 1.0 and 3.0 mg/kg Administration: IP; daily for 28 days Result: Significantly reduced tumor growth by 44.1% and 55.2% at 1 and 3 mg/kg, respectively.

[1]. Cilibrasi V, Spanò V, Bortolozzi R, et al. Synthesis of 2H-Imidazo[2',1':2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myeloid leukemia (AML) with FLT3/ITD mutations. Eur J Med Chem. 2022;235:114292.