NC-138

NC-138 is a potent and selective small molecule antagonist of the Prostaglandin E2 (PGE2) receptor subtype 4 (EP4), currently under development by Nippon Chemiphar. The EP4 receptor is a G protein-coupled receptor that plays a significant role in mediating the effects of PGE2, a lipid mediator often overproduced in various cancers. In the tumor microenvironment, PGE2-EP4 signaling promotes immune evasion by inhibiting the activity of cytotoxic T cells and natural killer cells while stimulating the expansion of regulatory T cells and myeloid-derived suppressor cells. By selectively blocking the EP4 receptor, NC-138 is designed to alleviate this immunosuppression, potentially restoring the host's anti-tumor immunity and providing synergistic effects when used in combination with other immunotherapies, such as PD-1/PD-L1 inhibitors. Clinical development has primarily focused on its application in patients with advanced solid tumors.