Cell experiment:

Human whole islets are incubated in assay buffer containing 2.8 mM glucose for 45 minutes at 37 ℃ to stabilize insulin secretion; islets are then treated with 11.2 mM glucose in the presence and absence of PF-5190457 for one hour at 37 ℃. Following incubation, samples are tested for the amount of insulin secreted into the media[1].

PF-5190457 is a potent and selective ghrelin receptor inverse agonist with a pKi of 8.36.

PF-5190457 has a superior balance of ghrelin receptor pharmacology and off-target selectivity[1].

PF-5190457 has excellent selectivity and demonstrates robust increases in glucose-stimulated insulin secretion in human whole and dispersed islets[1].

[1]. Bhattacharya SK, et al. Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin Receptor Inverse Agonist Clinical Candidate. ACS Med Chem Lett. 2014 Feb 24;5(5):474-9.