M5161

M5161 (also known as KAG-308) is an orally bioavailable, small molecule agonist of the prostaglandin E receptor 4 (EP4). Originally discovered by Asahi Kasei Pharma and licensed to Maruho for dermatological applications, M5161 was specifically developed to treat pruritus associated with atopic dermatitis. The EP4 receptor is a G protein-coupled receptor that mediates the effects of prostaglandin E2 (PGE2) and is involved in various physiological processes, including the regulation of inflammation and skin barrier integrity. By selectively activating EP4, M5161 was hypothesized to reduce the neurogenic and inflammatory components of itch. While it reached Phase IIa clinical trials for atopic dermatitis, the program appears to have been discontinued by Maruho for this indication, although the parent compound KAG-308 continues to be investigated by Asahi Kasei Pharma for other indications such as ulcerative colitis.