APD 668

SKU: orb1223917

Description

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%).

Key Properties

• CAS Number: 832714-46-2
• MW: 477.51
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₄FN₅O₅S
• SMILES: O=C(N1CCC(OC2=C3C(N(C4=CC=C(S(=O)(C)=O)C=C4F)N=C3)=NC=N2)CC1)OC(C)C
• Target: GPR
• Solubility: DMSO: 10 mM

Bioactivity

• 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%). 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 weeks. Result: Decreased the blood glucose and HbA1c levels at 30 mg/kg/day.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JNJ-28630368

Quick Database Links

Gene Symbol

GPR