Synonym
APD668; APD-668; APD 668; JNJ28630368; JNJ-28630368; JNJ 28630368.
IUPAC/Chemical Name
isopropyl 4-((1-(2-fluoro-4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)piperidine-1-carboxylate
InChi Key
XTRUQJBVQBUKSQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H24FN5O5S/c1-13(2)31-21(28)26-8-6-14(7-9-26)32-20-16-11-25-27(19(16)23-12-24-20)18-5-4-15(10-17(18)22)33(3,29)30/h4-5,10-14H,6-9H2,1-3H3
SMILES Code
O=C(N1CCC(OC2=C3C(N(C4=CC=C(S(=O)(C)=O)C=C4F)N=C3)=NC=N2)CC1)OC(C)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
APD668 is an agonist of G-protein coupled receptor GPR119, with EC50s of 2.7 nM and 33 nM for hGPR119 and rGPR119, respectively.
In vitro activity:
Thus, 3k (APD668) was shown to increase adenylate cyclase activation in HEK293 cells transfected with human GPR119 (but not in non-transfected cells) in a concentration-dependent manner with an EC50 of 23 nM. Compound 3k also enhanced insulin release from both rat and human isolated pancreatic islets in a glucose-dependent manner as previously observed for 1a.1 In a standard panel of around 80 known receptors and ion channels, 3k did not show any binding in excess of 50% of control to any other proteins at concentrations up to 10 μM.
Reference: Bioorg Med Chem Lett. 2011 May 15;21(10):3134-41. https://pubmed.ncbi.nlm.nih.gov/21444206/
In vivo activity:
To investigate the effect of APD668 on intestinal lipid absorption, this study conducted an oral fat tolerance test in normal mice. As shown in Fig. 1A, olive oil administration elevated plasma triglyceride levels in vehicle treated mice. Treatment with APD668 (30 mg/kg, p.o.) reduced the elevated plasma triglyceride levels at 2 h as compared to vehicle treated mice (P<0.001). Next, this study calculated area under curve and APD668 significantly inhibited the lipid excursion by approximately 42% in mice (Fig. 1A and B).
Reference: Eur J Pharmacol. 2017 Apr 15;801:35-45. https://pubmed.ncbi.nlm.nih.gov/28274625/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
49.8 |
104.25 |
|
| DMF |
25.0 |
52.35 |
|
| DMF:PBS (pH 7.2) (1:8) |
0.1 |
0.21 |
|
| Ethanol |
2.0 |
4.19 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
477.51
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Bahirat UA, Shenoy RR, Goel RN, Nemmani KV. 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. doi: 10.1016/j.ejphar.2017.02.043. Epub 2017 Mar 6. PMID: 28274625.
2. Semple G, Ren A, Fioravanti B, Pereira G, Calderon I, Choi K, Xiong Y, Shin YJ, Gharbaoui T, Sage CR, Morgan M, Xing C, Chu ZL, Leonard JN, Grottick AJ, Al-Shamma H, Liang Y, Demarest KT, Jones RM. 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. doi: 10.1016/j.bmcl.2011.03.007. Epub 2011 Mar 13. PMID: 21444206.
In vitro protocol:
1. Semple G, Ren A, Fioravanti B, Pereira G, Calderon I, Choi K, Xiong Y, Shin YJ, Gharbaoui T, Sage CR, Morgan M, Xing C, Chu ZL, Leonard JN, Grottick AJ, Al-Shamma H, Liang Y, Demarest KT, Jones RM. 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. doi: 10.1016/j.bmcl.2011.03.007. Epub 2011 Mar 13. PMID: 21444206.
In vivo protocol:
1. Bahirat UA, Shenoy RR, Goel RN, Nemmani KV. 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. doi: 10.1016/j.ejphar.2017.02.043. Epub 2017 Mar 6. PMID: 28274625.
2. Semple G, Ren A, Fioravanti B, Pereira G, Calderon I, Choi K, Xiong Y, Shin YJ, Gharbaoui T, Sage CR, Morgan M, Xing C, Chu ZL, Leonard JN, Grottick AJ, Al-Shamma H, Liang Y, Demarest KT, Jones RM. 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. doi: 10.1016/j.bmcl.2011.03.007. Epub 2011 Mar 13. PMID: 21444206.
1: Semple G, Ren A, Fioravanti B, Pereira G, Calderon I, Choi K, Xiong Y, Shin YJ, Gharbaoui T, Sage CR, Morgan M, Xing C, Chu ZL, Leonard JN, Grottick AJ, Al-Shamma H, Liang Y, Demarest KT, Jones RM. 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. doi: 10.1016/j.bmcl.2011.03.007. Epub 2011 Mar 13. PubMed PMID: 21444206.
