Definition
ChEBI: Benzoic acid, 4-[(1s)-1-[[5-chloro-2-(4-fluorophenoxy)benzoyl]amino]ethyl]- is an aromatic ether.
Biological Activity
ki: 3.16 nm: antagonizes e prostanoid receptor 4 (ep4).ki: 631 nm: antagonizes ep2.cj-42794, as a selective antagonist of ep4, less binds to ep2 and does not have binding affinity for ep1 or ep3. it displays minimal effect on numerous other receptors, channels, or enzymes. cj-42794 delays the healing of gastric ulcers, inhibiting the upregulation of vegf expression and angiogenesis. ep4, activated by prostaglandin e2 (pge2), is a g-protein-coupled receptor, which plays vital roles in bone formation and resorption, cancer, and atherosclerosis via elevating the second messenger cyclic amp (camp).
in vitro
cj-42794 exhibited remarkable binding activity to ep4 and suppressed pge2-triggered elevations of intracellular camp levels in a concentration-dependent fashion in hek293 cells overexpressing human ep4. moreover, cj-42794, concentration-dependently, reversed the inhibitory effects of pge2 on lipopolysaccharide-evoked tumor necrosis factor α production, which suggested that cj-42794 had excellent pharmacological properties used for exploring the physiological role of ep4 [1].
in vivo
male sprague-dawley rats and c57bl/6 mice were given subcutaneously 3 and 10 mg/kg for rats, 10 mg/kg for mice once daily for 7 or 14 days. compared to the controls, cj-42794, in a dose-dependent manner, impaired and delayed the gastric ulcer healing in rats and mice. cj-42794 markedly dampened the increase of vegf expression in ulcerated mucosa of the mouse stomach and the primary gastric fibroblasts of rat [2].
References
[1]. murase, a., taniguchi, y., tonai-kachi, h., nakao, k., & takada, j. in vitro pharmacological characterization of cj-042794, a novel, potent, and selective prostaglandin ep4 receptor antagonist. life sciences. 2008; 82(3-4): 226-232.
[2]. hatazawa, r., tanaka, a., tanigami, m., amagase, k., kato, s., ashida, y., & takeuchi, k. cyclooxygenase-2/prostaglandin e2 accelerates the healing of gastric ulcers via ep4 receptors. ajp: gastrointestinal and liver physiology. 2007; 293(4): g788-g797.
