GPR39 is a putative zinc-sensing G protein-coupled receptor (GPCR) related to the ghrelin/neurotensin peptide receptor subfamily which is implicated in cellular processes such as insulin secretion, protection from cell death, gastric emptying, and epithelial repair. GPR39-C3 is a potent and oral active GPR39 agonist with EC50s of 0.4 and 0.8 nM for rat and human receptors, respectively[1]. As a GPR39 positive allosteric modulator, GPR39-C3 activated cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment in HEK293-GPR39 cells. Moreover, GPR39-C3 induced dose- and time-dependent loss of response in cAMP production by second challenge of the compound[2]. In vivo, GPR39-C3 (30 mg/kg po) robustly induced acute GLP-1 levels in mice which is a PD marker[1].
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