EP4 antagonist DT-9081

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 antagonist DT-9081 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 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.