Butaprost is a chemical compound that functions as a selective agonist for the prostaglandin E receptor (EP2). It exhibits an EC50 of 33 nM and a Ki of 2.4 μM when interacting with the murine EP2 receptor. However, Butaprost demonstrates lower activity against murine EP1, EP3, and EP4 receptors. Furthermore, it effectively attenuates fibrosis by inhibiting the TGF-β/Smad2 signaling pathway [1] [2] [3].

Butaprost, at concentrations ranging from 1-100 nM over a period of 0.5-24 hours, significantly enhances Nur77 mRNA expression by approximately five-fold in hEP2-HEK293/EBNA cells, showing both dose- and time-dependency. The augmentation of Nur77 gene expression is mediated via the PKC pathway. Additionally, at a concentration of 50 μM for 24 hours, Butaprost mitigates TGF-β-stimulated fibronectin expression, Smad2 phosphorylation, and the epithelial-mesenchymal transition in Madin-Darby Canine Kidney (MDCK) cells. Western Blot analysis of HEK 293/EBNA cells, which stably express the human EP2 receptor, corroborates the five-fold increase in Nur77 mRNA expression after exposure to Butaprost.

Butaprost treatment (1-4 mg/kg; intraperitoneal injection; twice daily; for 7 days) effectively attenuates fibrosis development in male C57BL/6 mice (8 weeks of age; 21 g) subjected to unilateral ureteral obstruction surgery. This outcome is evidenced by the decreased gene and protein expression levels of α-smooth muscle actin, fibronectin, and collagen 1A1, indicating a significant mitigation of fibrosis.