Abstract The synthesis, enzymatic evaluation, and molecular modeling studies of new fluorogenic tetrapeptide-based substrates selective for caspase 8, having the general structure Ac-IETD–AXX, are described. Various fluorescent reporter groups (AXX), ie, 3-and 4-substituted coumarins and quinolin-2 (1H)-ones were synthesized by von Pechmann condensation. They were subsequently coupled with the caspase-8-selective tetrapeptide ...