[CAS NO. 832714-46-2] APD668
PRODUCTS SPECIFICATIONS [832714-46-2]
DESCRIPTION [832714-46-2]
Overview
| MDL | MFCD12032117 |
|---|---|
| Molecular Weight | 477.51 |
| Molecular Formula | C21H24FN5O5S |
| SMILES | O=C(OC(C)C)N(CC1)CCC1OC2=C3C(N(C4=CC=C(S(=O)(C)=O)C=C4F)N=C3)=NC=N2 |
1 Publications Citing Use of MCE
Summary
APD668 is a potent, selective and orally active agonist of G-protein coupled receptor GPR119 , with EC 50 s 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] .
IC50 & Target
|
hGPR119 2.7 nM (IC 50 ) |
rGPR119 33 nM (IC 50 ) |
CYP2C9 0.1 μM (Ki) |
hERG channel 3 μM (IC 50 ) |
In Vitro
APD668 increases adenylate cyclase activation in HEK293 cells transfected with human GPR119 in a concentration-dependent manner with an EC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male Zucker Diabetic Fatty (ZDF) rats (6 weeks old, 200-250 g) [1] |
| 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.
Did not develop diabetes, whereas the vehicle treated rats did. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 33.33 mg/mL ( 69.80 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0942 mL | 10.4710 mL | 20.9420 mL |
| 5 mM | 0.4188 mL | 2.0942 mL | 4.1884 mL |
| 10 mM | 0.2094 mL | 1.0471 mL | 2.0942 mL |
References
- [1] Semple G, et al. Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control. Bioorg Med Chem Lett. 2011 May 15;21(10):3134-41.
- [2] Bahirat UA, et, al. APD668, a G protein-coupled receptor 119 agonist improves fat tolerance and attenuates fatty liver in high-trans fat diet induced steatohepatitis model in C57BL/6 mice. Eur J Pharmacol. 2017 Apr 15;801:35-45.