FLT3-IN-18

FLT3-IN-18 is a potent and selective FLT3 inhibitor with an IC50 value of 0.003 µM. FLT3-IN-18 induces apoptosis and cell cycle arrest at G1 phase. FLT3-IN-18 inhibits FLT3 and STAT5 phosphorylation. FLT3-IN-18 has the potential for the research of acute myeloid leukemia (AML)[1].

Research Areas >> Cancer

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

IC50: 0.003 µM (FLT3)[1]

FLT3-IN-18(compound 7d) (0, 0.01, 0.1, 1, 10, 100 nM; 1h) 在 MV4-11 细胞中呈剂量依赖性降低 p-FLT3 Y589/591，p-FLT3 Y842，p-TAT5 Y694，p-ERK1/2 T202/Y204，p-MEK1/2 S217/221，p-AKT S473 的蛋白表达[1]。 FLT3-IN-18 (0, 0.01, 0.1, 1, 10, 100 nM; 24 h) 诱导细胞凋亡和细胞周期停滞在 G1 期[1]。 Cell Proliferation Assay[1] Cell Line: MV4-11, K562, MOLM-13, Kasumi-1, THP-1, U937, MCF-7 cells Concentration: 0-20 µM Incubation Time: 72 h Result: Inhibited cell growth with GI50s of 0.002, 0.380, 0.001, 0.513, 0.713, 0.664, 0.197 µM for MV4-11, K562, MOLM-13, Kasumi-1, THP-1, U937, MCF-7 cells, respectively. Western Blot Analysis[1] Cell Line: MV4-11 cells Concentration: 0, 0.01, 0.1, 1, 10, 100 nM Incubation Time: 1 h Result: Decreased the expression of p-FLT3 Y589/591, p-FLT3 Y842, p-TAT5 Y694, p-ERK1/2 T202/Y204, and p-MEK1/2 S217/221, p-AKT S473 in a dose-dependent manner. Cell Cycle Analysis[1] Cell Line: MV4-11 cells Concentration: 0, 0.01, 0.1, 1, 10, 100 nM Incubation Time: 24 h Result: Induced cell cycle arrest at G1 phase. Apoptosis Analysis[1] Cell Line: MV4-11 cells Concentration: 0, 0.01, 0.1, 1, 10, 100 nM Incubation Time: 24 h Result: Increased cleavage of the apoptotic marker protein PARP-1 (89 kDa fragment) and educed levels of the antiapoptotic protein Mcl-1.

FLT3-IN-18 (10 mg/kg; i.p.; once) 有效抑制大鼠的 FLT3 和 STAT5 磷酸化[1]。 Animal Model: Rats (MV4-11 xenografts)[1] Dosage: 10 mg/kg Administration: I.p.; once Result: Effectively inhibited FLT3-ITD autophosphorylation in MV4-11 xenografts, reduced STAT5 phosphorylation by over 95% after 24 h.

[1]. Gucký T, et al. Discovery of N2-(4-Amino-cyclohexyl)-9-cyclopentyl- N6-(4-morpholin-4-ylmethyl-phenyl)- 9H-purine-2,6-diamine as a Potent FLT3 Kinase Inhibitor for Acute Myeloid Leukemia with FLT3 Mutations. J Med Chem. 2018 May 10;61(9):3855-3869.