EP4 receptor antagonist YY001

An orally bioavailable small molecule antagonist of the prostaglandin E2 receptor EP4 subtype (PTGER4; EP4), with potential immunomodulating and antineoplastic activities. Upon oral administration, EP4 receptor antagonist YY001 selectively targets and binds to EP4, inhibiting the binding of the immunosuppressive prostaglandin E2 (PGE2) to EP4. This prevents the activation of EP4 and inhibits PGE2-EP4-mediated signaling. This inhibits PGE2-driven immune suppression by preventing the PGE2-mediated inhibition of anti-tumor immune effector cells in the tumor microenvironment (TME), such as natural killer (NK) cells, T lymphocytes, dendritic cells (DCs) and M1 macrophages, and blocking the PGE2-mediated increase in suppressive immune cells, such as myeloid derived suppressor cells (MDSCs), M2 macrophages, and regulatory T cells (Tregs). This activates an anti-tumor immune response and inhibits the proliferation of tumor cells in which the PGE2-EP4 signaling pathway is over-activated. EP4, a G protein-coupled receptor (GPCR) overexpressed in certain types of cancers, promotes tumor cell proliferation and invasion.