Grapiprant | EP4 Receptor antagonist

Grapiprant (415903-37-6) is a potent (Ki = 13 nM for human and 20 nM for rat) and selective prostaglandin EP4 receptor antagonist.1 It produces antihyperalgesic effects in animal models of pain, and has significant anti-inflammatory effects in a rat model of adjuvant-induced arthritis.2 EP4 receptors have been shown to be involved in PGE2 stimulation of Th1 differentiation and Th17 expansion revealing a potential role for PGE2 receptors in immunosuppression.3,4 Grapiprant/Pembrolizumab combination is in clinical trials for advanced or metastatic NSCLC adenocarcinoma.5

References/Citations

1) Nakao et al. (2007), CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties; J. Pharmacol. Exp. Ther. 332 686
2) Okumura et al. (2008), Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis; J. Pharm. Pharmacol. 60 7235
3) Chen et al. (2010), A novel antagonist of the prostaglandin E2 EP4 receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models; Br. J. Pharmacol. 160 292
4) Wang and DuBois (2016), Wang and DuBois (2016), The Role of Prostaglandin E2 in Tumor-Associated Immunosuppression; Trends Mol. Med. 22 1
5) NCT03696212 and NCT03658772