Epx16006 – a Highly Selective P2y2 Agonist Reduces Gastrointestinal Transit Time

Abstract

Purpose: To demonstrate that EPX-16006, a highly selective non-absorbed P2Y2 agonist, leads to fluid secretion in gut lumen and consequent reduction in gastrointestinal (GI) transit time. EPX-16006 is a novel drug candidate being developed for the treatment of chronic constipation and IBS-c. Methods: Total GI transit time of a non-absorbable meal was assessed in wild-type male Balb/c mice. Small intestinal and colonic transit was measured as the geometric center of a radioactive meal after oral gavage in mouse with EPX-16006 or vehicle. Fluid secretion was also evaluated in vivo in isolated colonic loops. Results: EPX-16006 dose-dependently reduced total GI transit time (Figure 1) and increased the production of feces and its water content (Figure 2, *P < 0.05, **P < 0.01), with no effect on small intestinal transit or on gastric emptying. EPX-16006 dose-dependently increased both colonic transit and colonic fluid secretion in mice.Figure 2Figure 1Conclusion: These results support the continued development of EPX-16006 as a novel drug candidate for patients suffering from chronic constipation. Because its site of action is restricted to the colon and it is not absorbed, EPX-16006 may have an improved safety and tolerability profile, including a reduced incidence of nausea and negligible systemic liabilities.