EP2/EP4/DP1 Antagonist OKN4395

**Semantic type:** Immunologic Factor|Pharmacologic Substance

**Definition:** An orally bioavailable, triple antagonist of the human prostaglandin E2 receptor subtypes 2 (EP2) and 4 (EP4), and the prostaglandin D2 receptor (DP1), with potential immunomodulating and antineoplastic activities. Upon oral administration, the EP2/EP4/DP1 antagonist OKN4395 selectively targets and binds to EP2 and EP4, thereby inhibiting the binding of the immunosuppressive prostaglandin E2 (PGE2) to EP2 and EP4. This prevents the activation of EP2 and EP4, and inhibits PGE2-EP2/EP4-mediated signaling. Also, OKN4395 binds to and inhibits DP1, thereby preventing prostaglandin D2 (PGD2) from binding to DP1, and blocking PGD2/DP1-mediated signaling. This inhibits PGE2/PGD2-driven immune suppression by preventing the PGE2/PGD2-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 increase in suppressive immune cells, such as myeloid derived suppressor cells (MDSCs), M2 macrophages, and regulatory T cells (Tregs). This restores anti-tumor immune responses and inhibits the proliferation of tumor cells in which the PGE2-EP2/4 and PGD2/DP1 signaling pathways are overactivated. Both pathways are overactivated in certain types of cancers and promote tumor cell proliferation, invasion, survival, metastasis, and immunosuppression.

**Synonyms:** - ACT 1002 4391 - EP2/EP4/DP1 Inhibitor OKN4395 - EP2/EP4/DP1 Prostanoid Receptors Antagonist OKN4395 - OKN 4395 - OKN4395