APD 668

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

APD668 是一种有效的 GPR119 激动剂，对 hGPR119 和ratGPR119 的 EC50 值分别为 2.7 nM 和 33 nM。

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%).

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.

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%). Animal Model:Male Zucker Diabetic Fatty (ZDF) rats (6 weeks old, 200-250 g)Dosage:10, 30 mg/kg Administration:P.o. once daily for 8 weeksResult:Decreased the blood glucose and HbA1c levels at 30 mg/kg/day.

JNJ-28630368

Cell Cycle/DNA Damage

GPR

GPR119

Metabolic Disease

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832714-46-2

477.51

C21H24FN5O5S

>98% (HPLC)

DMSO: 10 mM

O=C(N1CCC(OC2=C3C(N(C4=CC=C(S(=O)(C)=O)C=C4F)N=C3)=NC=N2)CC1)OC(C)C

isopropyl 4-((1-(2-fluoro-4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate .

(-20℃)

With Ice Pack

≥ 2 years