The prostaglandin E receptor 4 (EP₄) is one of four G protein-coupled receptors that mediate the actions of prostaglandin E₂ (PGE₂; Item No. 14010). Binding of PGE₂ to the EP₄ receptor causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption, cancer, and atherosclerosis.^1,2,3,4 KMN-80 is a substituted γ-lactam (pyrrolidinone) derivative of PGE₁ (Item No. 13010) that acts as a selective and potent agonist of EP₄ with an IC₅₀ value of 3 nM (IC₅₀ = 1.4 μM for EP₃ and > 10 μM for all other prostanoid receptors).⁵ In functional assays it has been shown to stimulate secreted alkaline phosphatase gene reporter activity in EP₄-transfected HEK293 cells with an EC₅₀ value of 0.19 nM, demonstrating >5,000 and 50,000-fold selectivity against EP₂ and TP, respectively.⁵ KMN-80 can induce the differentiation of bone marrow stem cells from both young and aged rats into osteoblasts in vitro (EC₅₀s = 20 and 153 nM, respectively) and exhibits favorable tolerability up to at least 10 μM, whereas the EP₄ agonist L-902,688 (Item No. 10007712) is highly cytotoxic at similar concentrations in these cells.⁶ KMN-80 has been used to repair calvarial defects in an in vivo rat craniomaxillofacial reconstruction model (rate of reduction in defect size equivalent to BMP-2 treated rats) and to promote bone formation in a rat incisor tooth socket model.⁶

≥98%

Store at -20℃

1.Li, M.,Thompson, D.D. and Paralkar, V.M. Prostaglandin E₂ receptors in bone formation. International Orthopaedics 31, 767-772 (2007).

2.Hawcroft, G.,Ko, C.W.S. and Hull, M.A. Prostaglandin E₂-EP₄ receptor signalling promotes tumorigenic behaviour of HT-29 human colorectal cancer cells. Oncogene 26, 3006-3019 (2007).

3.Babaev, V.R.,Chew, J.D.,Ding, L., et al. Macrophage EP₄ deficiency increases apoptosis and suppresses early atherosclerosis. Cell Metabolism 8, 492-501 (2008).

4.Konya, V.,Marsche, G.,Schuligoi, R., et al. E-type prostanoid receptor 4 (EP₄) in disease and therapy. Pharmacology & Therapeutics 138(3), 485-502 (2013).

5.Barrett, S.D.,Ciske, F.L.,Endres, G.W., et al. Novel Potent Lactam Acetylene EP₄ Agonists Stimulate Alkaline Phosphatase Production and Differentiation in Bone Marrow Cells. (2014).

6.O’Malley, J.,Uzieblo, A.,Germain, B.D., et al. Development of a Novel Prostaglandin EP₄ Agonist Which Stimulates Local Bone Formation in vivo. (2014).