Kmn-80

KMN-80, a derivative of PGE1 (HY-B0131), is a selective and potent agonist of EP4 receptor with an IC50 and a Ki of 3 nM and 2.35 nM, respectively. KMN-80 is against EP3 receptor with an IC50 of 1.4 μM and >10 μM for all other prostanoid receptors[1].

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

Research Areas >> Metabolic Disease

EP4 Receptor:3 nM (IC50)

EP3 receptor:1.5 μM (IC50)

h-EP4:2.349 nM (Ki)

hEP3A Receptor:880 nM (Ki)

KMN-80 is tested for binding of EP4 receptor and for activation of the rat EP2 and EP4 receptors, exhibits a Ki of 1.11 nM for rat EP4 receptor, EC50 values of 2.66 nM and 0.17 nM for rat EP4 receptor cAMP levels and rat EP4 receptor CREB activation, respectively[1]. BMCs are isolated from young female rats are treated once at plating with varying doses of KMN-80 and ALP enzyme activity determined on day 9. KMN-80 (0-100 nM) shows ALP EC50 values significant different than those corresponding to PGE2 and PGE1, the EC50 values are 82.1 nM and 29.3 nM in activation of ALP enzyme activity in young female rat BMCs or old female or young male rat BMCs, respectively[1]. KMN-80has 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[2]. 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 is highly cytotoxic at similar concentrations in these cells[2]. KMN-80 binds to human EP receptor subtypes with Ki values of 880 nM and 2.349 nM for hEP3 and hEP4, respectively[2].

[1]. M Li, et al. Prostaglandin E(2) Receptors in Bone Formation. Int Orthop

[2]. Thomas A Owen, et al. KMN-159, a Novel EP 4 Receptor Selective Agonist, Stimulates Osteoblastic Differentiation in Cultured Whole Rat Bone Marrow. Gene. 2020 Jul 20;748:144668.