APD 668

APD668 is a potent GPR119 agonist with EC50 of 2.7 nM and 33 nM for hGPR119 and ratGPR119 respectively. (In Vitro) :APD668 increases adenylate cyclase activation in HEK293 cells transfected with human GPR119 in a concentration-dependent manner with an EC50 of 23 nM.APD668 is highly bound to plasma proteins of male and female cynomolgus monkeys and humans (99%), but is less extensively bound to male (93.0%) and female (96.6%) rats. (In Vivo) :APD668 (10-30 mg/kg; p.o. once daily for 8 weeks) significantly reduces blood glucose and glycated hemoglobin (HbA1c) levels, with no desensitization of the acute drug response.APD668 (1-10 mg/kg; a single p.o.) markedly reduces blood glucose levels during oral glucose tolerance test in a dose-dependent manner in mice.APD668 (0.08 mg/kg/min; i.v.) shows no effect during euglycemic condition, but significantly stimulates insulin release when blood glucose levels are raised to approximately 300 mg/dl in a hyperglycemic clamp model in the Sprague-Dawley rat.APD668 (p.o.) exhibits rapid to moderate absorption (tmax≤2 h) in mice, rats, and monkeys, but slower in dogs (tmax=6 h), and moderate to good absolute oral bioavailability (44-79%) in mice, rats, and monkeys, but lower in dogs (22%) .