Therapeutics: Glucagon-like protein-1 (GLP-1); GLP-1 receptor (GLP-1R; GLP1R)

Cell culture and mouse studies have identified a positive allosteric modulator (PAM) of GLP1R that could help treat type 2 diabetes and PD-related catalepsy. In a GLP1R-expressing human cell line, the lead PAM potentiated GLP-1 activation with an EC50 value of 1.3 μM. In primary mouse pancreatic islets, the compound plus Byetta exenatide increased insulin secretion compared with Byetta alone. In a mouse model of haloperidol-induced catalepsy, the compound decreased catalepsy compared with vehicle. Ongoing work includes optimizing the potency and metabolic profile of the lead compound...