Prostaglandin E₂ (PGE₂) is known to cause bone formation with its activation of the EP₄ receptor being primarily responsible for its anabolic actions (Pagkalos et al., Curr. Mol. Pharmacol., 2012). Current bone anabolic therapies for local application are typically protein-based and have relatively short shelf lives. In addition to being expensive, safety concerns are raised by the morphogenic activity associated with some of these therapies, limiting their potential use in orthopedic and other local applications. We have developed a series of novel difluorolactam EP₄ receptor agonists in order to alleviate these issues in a potential therapeutic agent (Barrett et al., J. Med. Chem., 2019).

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To cite this poster: Owen, T.A., Patel, C., Cahill, A., et al. Release of the EP₄ receptor agonist KMN-159 from scaffolds in vitro. Poster presented at: ORS 2020 Annual Meeting; February 8-11, 2020; Phoenix, AZ.

​The work presented here is from the ongoing characterization of our lead compound, KMN-159, which shows high selectivity for EP₄ binding, excellent potency for EP4 activation, potent stimulation of osteoblastic differentiation in unfractionated bone marrow cells (BMCs), and remarkable chemical stability.

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To cite this poster: Owen, T., Wei, S., Birmingham, K., et al. Biochemical and molecular characterization of the osteoblastic differentiation of rat bone marrow stem cells treated with KMN-159, a novel selective EP₄ prostaglandin receptor agonist. Poster presented at: ASBMR 2019 Annual Meeting; September 20-23, 2019; Orlando, FL.

• Cayman scientists deliver KMN-159, a novel, selective EP₄ receptor agonist with lower entropic costs of binding and increased affinity than other known agonists.​
• ​KMN-159 was identified from a series of stereoisomerically pure EP₄ receptor-selective agonists evaluated by docking onto a rat EP₄ receptor model using AutoDock and Schrödinger.
• Continued development of novel, selective EP₄ agonists will further elucidate the role of this receptor and aid in the identification of novel therapeutics for bone growth, cardiovascular function, and disease.​