Our recent work published in J. Med. Chem. 2026, 69, 4, 3833–3851 reports the design and synthesis of dual-charged naltrexamine amide derivatives as ligands of the κ-opioid receptor. Through systematic amide coupling of synthetic amino acids to naltrexamine, we generated a focused compound library and identified ligands with pronounced G-protein signaling bias. Using the recently developed MDPath approach, we were able for the first time to reveal mechanistic pathways linking ligand binding to biased receptor signaling.