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. It inhibits FLT3 autophosphorylation and induces a dose-dependent cytotoxic response (mean IC50 = 1 μM). AKN-028 acetate also induces apoptosis by activation of caspase 3 and can be used in acute myeloid leukemia (AML) research [1].

AKN-028 acetate (0.1 nM-100 μM; 15 h; mouse embryonal fibroblasts and human acute megakaryoblastic leukemia M07 cells) inhibits FLT3 and KIT autophosphorylation in a dose-dependent manner [1]. AKN-028 acetate (10 μM; 72 h; tumor cell lines) is cytotoxic to AML cell lines and induces apoptosis in the AML cell line MV4-11 [1]. In cytotoxicity assays, AKN-028 acetate showed the highest cytotoxic activity in MV4-11 and MOLM-13 (IC 50 <50 nM), followed by three other AML cell lines (IC 50 = 0.5-6 μM) [1]. Western Blot Analysis demonstrated inhibition of FLT3 and KIT autophosphorylation in mouse embryonal fibroblasts overexpressing FLT-wt, FLT3-TKD, or FLT3-ITD, and in human acute megakaryoblastic leukemia M07 cells overexpressing KIT, after 15 hours of incubation (0.1 nM-100 μM) [1].

AKN-028 acetate, administered at a dosage of 15 mg/kg via subcutaneous injection twice daily for a duration of six days, effectively inhibits the growth of primary AML and MV4-11 cells in male C57 black mice with MV4-11 xenografts, without impacting the animals' body weight [1].