KMN-80

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).¹ 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.¹ 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.² 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.²

WARNING This product is not for human or veterinary use.

1. 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).

2. 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).

Barrett, S.D., Holt, M.C., Kramer, J.B., et al. Difluoromethylene at the γ-lactam α-position improves 11-deoxy-8-aza-PGE₁ series EP₄ receptor binding and activity: 11-deoxy-10,10-difluoro-8-aza-PGE₁ analog (KMN-159) as a potent EP₄ agonist. J. Med. Chem. 62(9), 4731-4741 (2019).