EP4 Receptor Antagonists – Target Pipeline List
Target: Prostaglandin E2 (PGE2) type EP4 receptor
This Target Pipeline list provides an overview of small molecules targeting the EP4 receptor of PGE2 in the tumor microenvironment in preclinical or clinical development for treatment of solid tumors.
Prostaglandin E2 (PGE2) has been shown to contribute to an immunosuppressive environment in cancer by enhancing the activity of regulatory immune cells and suppressing the activity of effector immune cells. EP4 is a high-affinity receptor of PGE2 and is known to facilitate these immunosuppressive activities.
It is known that activating EP4 receptors causes monocytes to differentiate into M2 macrophages which have immuno-suppressive effects. As demonstrated in preclinical studies, inhibiting EP4 receptors reduces M2 macrophages, and by increasing M1 macrophages which activate immune response, antitumor effects can be expected.
In preclinical studies, inhibition of EP4 has been shown to boost the immune response through modulation of multiple immune cell types, and in combination with checkpoint inhibitors has yielded significant reduction in tumor growth relative to either agent alone.
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