HSN608

HSN608 is a **novel small molecule inhibitor** designed to target both **RET solvent-front mutations** and **FLT3 mutations** implicated in resistance to current therapies. It is an **alkynyl nicotinamide-based compound** with potent inhibitory activity against RET G810 solvent-front mutants, the V804M gatekeeper mutant, and drug-resistant secondary mutations of FLT3, including FLT3ITD and FLT3 secondary mutations found in acute myeloid leukemia (AML). HSN608 demonstrates antileukemic activity, especially against relapsed/refractory AML and AML with combined epigenetic mutations such as TET2 along with FLT3ITD. In preclinical models, it showed **superior or comparable efficacy** to existing RET and FLT3 inhibitors, including gilteritinib. It also exhibits favorable pharmacokinetics, such as oral bioavailability and sufficient plasma concentrations relative to its in vitro inhibitory concentration[1][3][5][7][9].