Discovery of TRD‐93 as a novel <scp>DRAK2</scp> inhibitor

Death-associated protein kinase-related apoptosis-inducing kinase 2 (DRAK2) has become a promising target for drug development. In search of novel and selective DRAK2 inhibitor motif, in vitro screen assay was established performed using in-house chemical libraries. After through hit triage procedure, N2-(3,5-dichlorophenyl)-5-fluoro-N4-methylpyrimidine-2,4-diamine (1) selected as initial with structural novelty drug-likeness. During validation, structure–activity relationship 1 thoroughly disclosed TRD-93 finally validated inhibition. is small (mw = 290) but selectively potent to (IC50 0.16 μM) over other kinases including DAPK family kinases. Molecular binding model study also discussed.