HSN748

HSN748 is a novel, nicotinamide-based small molecule inhibitor designed to target drug-resistant forms of acute myeloid leukemia (AML). It functions as a type II inhibitor of the FMS-like tyrosine kinase 3 (FLT3) and its mutants, including those that confer resistance to current FLT3 inhibitors. HSN748 was engineered using the three-dimensional atomic structure of FLT3 to fit precisely into the active site of both wild-type and mutant forms, effectively blocking enzymatic activity essential for AML cell survival. Preclinical studies have demonstrated that HSN748 exhibits potent antileukemic activity at subnanomolar concentrations against drug-resistant AML models, outperforming FDA-approved FLT3 inhibitors such as gilteritinib in vivo. The compound also retains inhibitory activity against ABL1, VEGFRs, and PDGFRα/β but shows reduced off-target effects compared to ponatinib due to loss of activity against c-Src and FGFRs—potentially offering an improved safety profile[1][2][7]. Developed by researchers at Purdue University in collaboration with Indiana University School of Medicine, HSN748 is currently patent-pending and licensed by KinaRx for further clinical development[4][6][8].