As of today, three kappa opioid receptor (KOR) agonists, nalfurafine (TRK-820, Remich®), difelikefalin (CR845, KorsuvaTM), and nalbuphine (HaduvioTM, KOR agonist and a weak mu opioid receptor partial agonist) (Figure 1) are in clinical studies for treating chronic itch of chronic kidney disease, cholestatic liver disease, and atopic dermatitis [1,2,3,4]. The gene discussed is OPRK1; the disease is Cholestatic liver disease.