E7046 is a potent and selective antagonist that potently competes with PGE2 binding to the type 4 prostaglandin E2 (PGE2) receptor EP4 [1,2].
Prostaglandin E2 receptor 4 (EP4) is a prostaglandin receptor for prostaglandin E2 (PGE2) implicated in various physiological and pathological responses in animal models and humans [3].
In vivo: In APCMin/+ mice, daily oral administration of E7046 slowed down the growth of established subcutaneous tumors and significantly delayed the recurrence of tumors after surgical resection. E7046 significantly reduced the combined colon polyp area and the size of individual polyps without influencing the total polyp number. E7046 exhibited great activity against colon and small intestine tumors [1]. E7046 delayed the growth of multiple syngeneic murine tumor types. E7046 showed no effect on tumor cell viability in vitro [2]. In the CT26 model, treatment with E7046 and anti-PD1 inhibited tumor growth. In the 4T1 model, E7046 in combination with anti-CTLA4 resulted in a nearly complete tumor growth inhibition [4].
References:
[1] Albu D I, Wu J, Huang K, et al. Abstract B198: Pharmacological profile of the PGE2 EP4 receptor antagonist E7046[J]. 2015.
[2] Albu D I, Huang K C, Wu J, et al. Abstract B034: Preclinical immune antitumor activity of myeloid-targeting E7046 and Treg depleting E7777[J]. 2016.
[3] Negishi M, Sugimoto Y, Ichikawa A. Prostaglandin E receptors[J]. Journal of lipid mediators and cell signalling, 1995, 12(2-3): 379-391.
[4] Bao X, Albu D, Huang K C, et al. Combination of EP4 antagonist and checkpoint inhibitors promotes anti-tumor effector T cells in preclinical tumor models[J]. Journal for immunotherapy of cancer, 2015, 3(2): P350.
