Prostaglandin E2 (PGE2) receptors (EP4-R) are a particularly promising anti-inflammatory and antinociceptive target. Prostaglandin E2 (PGE2) is responsible for inflammatory symptoms. There are at least 4 subtypes of PGE2 receptors, EP1-EP4. EP4-R is responsible for mediating PGE2-induced proliferative and nociceptive effects. Antagonizing EP4 receptor signaling not only blocks PGE2-induced proliferation of endometrial cells but also modulates anti-inflammatory activities and attenuated inflammatory pain. Therefore, antagonism of EP4-R signaling presents a particularly promising approach for the treatment of endometriosis-associated inflammatory pain.

In this study, researchers discovered BAY 1316957. BAY-1316957 is a potent and selective human prostaglandin E2 receptor subtype 4 (hEP4-R) antagonist for the treatment of endometriosis. BAY 1316957 exhibits excellent drug metabolism and pharmacokinetic properties. Notably, treatment with BAY 1316957 leads to prominent and rapid pain relief and significant improvement of the patient’s quality of life.

Oral administration of BAY 1316957 (5 mg/kg) 60 min prior to dmPGE2 injection significantly increases paw withdrawal thresholds. Oral treatment with BAY 1316957 significantly reduces pain-related paw withdrawal behavior in the rat upon mechanical stimulation of the dmPGE2-treated hind paw. BAY-1316957 has excellent drug metabolism and pharmacokinetic properties and can be used for endometriosis research.

All in all, BAY-1316957 is a potent, selective, and orally active prostaglandin E2 receptor subtype 4 (EP4-R) antagonist with an IC50 of 15.3 nM for human EP4-R. BAY 1316957 is suitable for further development for the treatment of endometriosis in women.

Stefan Bäurle, et al. Identification of a Benzimidazolecarboxylic Acid Derivative (BAY 1316957) as a Potent and Selective Human Prostaglandin E2 Receptor Subtype 4 (hEP4-R) Antagonist for the Treatment of Endometriosis. J Med Chem. 2019 Mar 14;62(5):2541-2563.