Definition

A small molecule, orally bioavailable antagonist of the prostaglandin E2 receptor subtype 4 (PTGER4; EP4), with potential immunomodulating and antineoplastic activities. Upon oral administration, EP4 antagonist CR6086 selectively targets and binds to EP4, thereby inhibiting the binding of the immunosuppressive prostaglandin E2 (PGE2) to EP4 and preventing the activation of EP4. This inhibits PGE2-EP4-mediated signaling and inhibits the proliferation of tumor cells in which the PGE2-EP4 signaling pathway is overactivated. In addition, EP4 inhibition prevents the activity of tumor-associated myeloid cells (TAMCs) in the tumor microenvironment (TME) by inhibiting interleukin-23 (IL-23) production and the IL-23-mediated expansion of T-helper 17 (Th17) cells. EP4, a prostanoid receptor, is a G protein-coupled receptor that is expressed in certain types of cancers; it promotes tumor cell proliferation and invasion.