In vitro activity: TGR5 Receptor Agonist is a novel, potent and synthetic small molecule agonist of TGR5(G-protein coupled receptor19, GPCR19) agonist, it showed improved potency in the U2-OS cell assay with pEC50 of 6.8 and in melanophore cells with pEC50 of 7.5. TGR5 Receptor Agonist is 3-aryl-4-isoxazolecarboxamide analog identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. TGR5 Receptor Agonist demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. G-protein coupled receptor is potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications.

Kinase Assay: TGR5 Receptor Agonist was profiled against more than 100 in-house and external 7TM, ion channel, enzyme, transporter, and nuclear hormone receptor selectivity assays, including FXR, another bile acid receptor, and showed significant response only in secretion of the pro-inflammatory cytokine TNFalpha (pIC50 = 6.8) in human primary monocytes following stimulation with LPS (lipopolysaccharide). In addition, TGR5 Receptor Agonist has good physicochemical properties and no measurable activity against three of the common cytochrome P450 (CYP450) isoforms (1A2, 2C9, and 2D6) or hERG dofetilide binding (pIC50<4.3).

Cell Assay: TGR5 Receptor Agonist showed improved potency in the U2-OS cell assay with pEC50 of 6.8 and in melanophore cells with pEC50 of 7.5.