AKN-028 acetate, a novel tyrosine kinase (TK) inhibitor, is a potent, orally active FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor with an IC 50 value of 6 nM. AKN-028 acetate inhibits FLT3 autophosphorylation. AKN-028 acetate induces dose-dependent cytotoxic response (mean IC 50 =1 μM). AKN-028 acetate induces apoptosis by 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 (IC 50 <50 nM), followed by the three other AML cell lines (IC 50 =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.