APD668

APD668 is a potent, selective and orally active agonist of G-protein coupled receptor GPR119, with EC₅₀s of 2.7 nM and 33 nM for hGPR119 and rGPR119, respectively. APD668 shows no significant inhibition of any of the five major CYP isoforms with the exception of CYP2C9 (K_i=0.1 μM). APD668 can be used for the research of steatohepatitis and diabetes^[1][2]. 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^[1].
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^[1].
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^[1].
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^[1].
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^[1].
APD668 (p.o.) exhibits rapid to moderate absorption (t_max≤2 h) in mice, rats, and monkeys, but slower in dogs (t_max=6 h), and moderate to good absolute oral bioavailability (44-79%) in mice, rats, and monkeys, but lower in dogs (22%)^[1].