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Research tools

APD668

GPR119 agonist (EC50 2.7 nM at the human receptor), the OEA receptor; no activity at CB1 or CB2 found.

Unscheduled
Level of detail

C₂₁H₂₄FN₅O₅S

CID 11705608

Family
ECS pharmacological toolOther target
Molar mass
477.50 g/mol

Updated on

In plain terms

APD668 is an entirely synthetic molecule, developed by a US company (Arena Pharmaceuticals) and described in 2011 as a drug candidate for type 2 diabetes. It is not a cannabinoid and is not found in hemp: it activates a receptor called GPR119, which is also stimulated by a lipid close to anandamide, oleoylethanolamide. No result in humans was found.

Receptors and activity

Target network

  • Activates

The lower the cited value, the closer the target sits to APD668: one ring per factor of 100. A target with no measured value stays on the edge.

Cited values

  1. GPR119AgonistEC50 = 2.7 nM · human76 out of 100

    Semple et al., Bioorg Med Chem Lett 2011 (values read from ChEMBL, document CHEMBL1773020) (new tab) · melanophore assay on human GPR119 (2.7 nM; rat 33 nM); 23 nM at human GPR119 in HEK293 cells; Emax 89% relative to AR231453; values read from ChEMBL, document CHEMBL1773020

Bar length follows the measured value (Ki, Kd, EC50 or IC50), on one scale shared by every entry, from 100 µM to 0.1 nM. A target with no cited value has no bar.

Measured effects

Not characterised. No placebo-controlled human trial has measured the effects of APD668, so no level is shown.

Levels computed from placebo-controlled human trials: difference from placebo on 100, at the dose and route stated. Read the method

Pharmacology

APD668 is an agonist of the GPR119 receptor (Gαs), expressed mainly in pancreatic islet cells and intestinal enteroendocrine cells. Semple and colleagues at Arena Pharmaceuticals described it in 2011 as compound 3k, derived from the prototype agonist AR231453 by introducing a pyrazolopyrimidine core and then a piperidine ether capped with a carbamate: EC50 2.7 nM at the human receptor and 33 nM at the rat receptor in a melanophore assay. Chronic treatment lowered blood glucose and glycated haemoglobin in ZDF rats over several weeks, and it was reported as the first compound with this mechanism progressed into clinical development for diabetes. The link with the endocannabinoid system is indirect: the endogenous ligand proposed in 2006 is oleoylethanolamide, an N-acylethanolamine like anandamide (Overton et al. 2006), and the structure of GPR119 bound to APD668 (Xu et al. 2022) shows a binding mode very similar to that of lysophosphatidylcholine. In mice, a single dose of APD668 inhibited intestinal triglyceride absorption after an acute fat load and increased incretin secretion and total PYY, and chronic oral administration to mice fed a high trans-fat diet improved hepatic parameters (ALT, AST, liver weight, steatosis) (Bahirat et al. 2017); combined with linagliptin, the effect on several of these parameters was more marked (Bahirat et al. 2018, 2019). These are preclinical results; no result in humans was found.

Key sources.

History

Source
An entirely synthetic molecule; no natural occurrence was found in the sources consulted. It was designed in a medicinal chemistry programme at Arena Pharmaceuticals (San Diego) from the prototype agonist AR231453: the series combines a pyrazolopyrimidine core and a piperidine ether capped with a carbamate (Semple et al. 2011).

Origin

Research tool

No biological pathway: APD668 is a synthetic compound (a pyrazolopyrimidine bearing a piperidine carbamate ether), unrelated to the plant cannabinoid pathway.

Classification

Family, origin and source verification

Family

ECS pharmacological tool › Other target

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

No dedicated article.

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 (new tab)PMID 21444206
  2. Overton HA et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab, 2006 (new tab)PMID 16517404
  3. Xu P et al. Structural identification of lysophosphatidylcholines as activating ligands for orphan receptor GPR119. Nat Struct Mol Biol, 2022 (new tab)PMID 35970999
  4. 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 (new tab)PMID 28274625
  5. Bahirat UA et al. Co-administration of APD668, a G protein-coupled receptor 119 agonist and linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in mice fed on a high trans-fat diet. Biochem Biophys Res Commun, 2018 (new tab)PMID 29203247
  6. Bahirat UA et al. Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes. Med Mol Morphol, 2019 (new tab)PMID 29959534
  7. PubChem, APD668, CID 11705608 (identifiers and properties) (new tab)

Identifiers

Names

IUPAC name
propan-2-yl 4-[1-(2-fluoro-4-methylsulfonylphenyl)pyrazolo[5,4-d]pyrimidin-4-yl]oxypiperidine-1-carboxylate
Other names
APD-668 · APD 668 · JNJ-28630368

Identifiers

Formula
C₂₁H₂₄FN₅O₅S
PubChem CID
11705608(new tab)
InChIKey
XTRUQJBVQBUKSQ-UHFFFAOYSA-N
SMILES
CC(C)OC(=O)N1CCC(CC1)OC2=NC=NC3=C2C=NN3C4=C(C=C(C=C4)S(=O)(=O)C)F

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.