IC50: 6 nM (FLT3), 140 nM (CLK1), 220 nM (RPS6KA), 520 nM (VEGFR2), and 120 nM (FGFR2)[1]
AKN-028 acetate, a novel tyrosine kinase (TK) inhibitor, is a potent, orally active FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor with an IC50 value of 6 nM. AKN-028 acetate inhibits FLT3 autophosphorylation. AKN-028 acetate induces dose-dependent cytotoxic response (mean IC50=1 μM). AKN-028 acetate induces apoptosisby activation of caspase 3. AKN-028 acetate can be used in research of acute myeloid leukemia (AML)[1].
AKN-028 (0.1 nM-100 μM; 15 h; mouse embryonal fibroblasts and human acute megakaryoblastic leukemia M07 cells) acetate inhibits FLT3 and KIT autophosphorylation in a dose-dependent manner[1].
AKN-028 (10 μM; 72 h; tumor cell lines) acetate is cytotoxic to AML cell lines and induces apoptosis in the AML cell line MV4-11[1].
Cell Cytotoxicity Assay[1]
| Cell Line: | Tumor cell lines |
| Concentration: | 10 μM |
| Incubation Time: | 72 hours |
| Result: | Had cytotoxic activity was highest in MV4-11 and MOLM-13 (IC50<50 nM), followed by the three other AML cell lines (IC50=0.5-6 μM). |
Western Blot Analysis[1]
| Cell Line: | Mouse embryonal fibroblasts either overexpressing FLT-wt, FLT3-TKD or FLT3-ITD and human acute megakaryoblastic leukemia M07 cells overexpressing KIT |
| Concentration: | 0.1 nM-100 μM |
| Incubation Time: | 15 hours |
| Result: | Inhibited FLT3 and KIT autophosphorylation. |
AKN-028 (15 mg/kg; i.h.; twice daily, for 6 days; male C57 black mice with MV4-11 xenografts) acetate inhibits growth of primary AML and MV4-11 cells in mice[1].
| Animal Model: | Male C57 black mice with MV4-11 xenografts[1] |
| Dosage: | 15 mg/kg |
| Administration: | Subcutaneous injection; twice daily, for 6 days |
| Result: | Inhibited tumor growth and did not affect body weight. |