1. Academic Validation
  2. Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists

Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists

  • ACS Med Chem Lett. 2013 Jul 11;4(7):616-621. doi: 10.1021/ml400112h.
Thota Ganesh 1 Jianxiong Jiang Rangaiah Shashidharamurthy Ray Dingledine
Affiliations

Affiliation

  • 1 Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia 30322, United States.
Abstract

Prostanoid receptor EP2 is emerging as a novel target for development of anti-inflammatory drugs for the treatment of chronic neurodegenerative and peripheral diseases; however, the availability of EP2 antagonist probes for exploration of peripheral disease models is very limited. We now report identification and characterization of a novel chemical class of compounds that show nanomolar potency and competitive antagonism of the EP2 receptor. A compound in this class, TG6-129, showed prolonged plasma half-life and did not cross the blood brain barrier. This compound also suppressed the induction of inflammatory mRNA markers in a macrophage cell line upon activation of EP2. Thus, this compound could be useful as a probe for a variety of peripheral chronic inflammatory diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease, in which EP2 appears to play a pathogenic role.

Keywords

EP2 antagonist; EP2 receptor; Inflammation; acrylamides; cytokines; macrophage.

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