摘要Natural products(NPs)make a major contribution to drug development,offering a huge molecule pool for drug leads.Nevertheless,the pharmaceutical industry and academy have declined their enthusiasm to NPs research since the great challenges in elucidating the complex component and intricate mech-anism of NPs.Here,we introduce an efficient fragment-based target research(FBTR)approach for pharmacology study and optimization of NPs.Focusing on the core fragment within the molecules of NPs,we screen the outstanding activity that be triggered,and corresponding target.Finally,drug optimization was carried out around the molecules that obtaining the activity-related core fragment and verified both in vitro and in vivo.With this approach,we obtained an optimized NPs named Erigeron breviscapus polyphenols(EBP)with definite target.After optimization,EBP plus(EBPP)not only trigger immunogenic cell death(ICD)of glioblastoma(GBM)cells effectively by targeting to Cys105 amino acid site of Fas-associating protein with a novel death domain(FADD)protein,but also prolong the survival of GBM mice by an average of 17.6 days.Significantly,our investigation presents an approach for addressing challenges in NPs development and opening up new opportunities for drug discovery.Our findings demonstrate the utility of FBTR in exploring the function of NPs,revealing the target,and advancing drug optimization for stronger clinical translation.