Fig. 2: Chemical structures of compounds used in our studies.

AG10 and compound 1 are selective TTR ligands. Naloxone is an opioid antagonist that crosses the blood-brain barrier (BBB). MNTX and naloxegol are PAMORAs approved to treat OIC. AG10-L1-Nal and AG10-L2-Nal are conjugates of AG10 and naloxone using linkers (L1 and L2) of different lengths. Oxycodone is an analgesic opioid agonist. AG10-L2-Oxy is a conjugate of AG10 and oxycodone.