| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
β2 adrenoceptor Microbial Metabolite Human Endogenous Metabolite. Myocardial ischemia/reperfusion (I/R) injury is closely related to cardiomyocyte apoptosis. Stimulating β2 adrenergic receptor (β2AR) can effectively combat cardiomyocyte apoptosis. Previous studies demonstrate that the gut microbial metabolite phenylacetylglycine (PAGly) can stimulate β2AR. However, the effect of PAGly on myocardial I/R injury remains unknown.
Phenylacetylglycine targets the β2 adrenergic receptor (β2AR), a G protein-coupled receptor that mediates the effects of catecholamines such as epinephrine. Activation of β2AR by phenylacetylglycine stimulates intracellular signaling pathways, including the cAMP/PKA pathway, which can modulate cardiac function, inflammation, and apoptosis. β2AR activation has been shown to protect against cardiomyocyte apoptosis and reduce ischemia/reperfusion injury. Phenylacetylglycine's ability to activate β2AR makes it a compound of interest for studying the role of gut microbial metabolites in cardiovascular protection. The compound may also interact with other receptors or pathways as an endogenous metabolite. |
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| ln Vitro |
In neonatal mouse cardiomyocytes (NMCM), phenylacetylglycine (10-100 μM; 30 minutes prior to H/R injury) decreases deoxygenated (H/R) injury-induced apoptosis and activates Gαi and Gαs signaling [1].
In vitro, phenylacetylglycine activates the β2 adrenergic receptor, as demonstrated by its ability to stimulate cAMP production in cells expressing β2AR. The compound protects against cardiomyocyte apoptosis in models of ischemia/reperfusion injury by activating β2AR and its downstream signaling pathways. Phenylacetylglycine's protective effects are mediated through the activation of the cAMP/PKA pathway, which inhibits apoptosis and promotes cell survival. In cell-based assays, phenylacetylglycine has been shown to reduce markers of oxidative stress and inflammation, suggesting additional cytoprotective effects. The compound's in vitro activities are concentration-dependent, with effects observed at physiologically relevant concentrations. |
| ln Vivo |
PAGly significantly suppressed H/R injury-induced apoptosis in NMCMs and inhibited apoptosis in myocardial I/R injured mice in vivo. We verified that PAGly activated the anti-apoptotic Gαi/PI3K/AKT signaling cascade in NMCMs via stimulating β2AR signaling. Continuous administration of PAGly at an appropriate dose could inhibit apoptosis and reduce the infarct size resulting from I/R injury in mice. However, high-dose PAGly treatment was associated with a higher mortality rate. Moreover, we demonstrated that Aspirin reduced the infarct size and the high mortality caused by high doses of PAGly in I/R injured mice [1].
In vivo, phenylacetylglycine has demonstrated protective effects against ischemia/reperfusion-induced cardiac injury in animal models. Administration of phenylacetylglycine reduces infarct size, improves cardiac function, and decreases markers of apoptosis and inflammation in the heart. The compound's cardioprotective effects are mediated through β2AR activation, as they are blocked by β2AR antagonists. Phenylacetylglycine is a gut microbial metabolite that can enter the circulation and modulate host physiology, highlighting the importance of the gut-heart axis. The compound's in vivo efficacy supports its potential as a therapeutic agent for ischemic heart disease. |
| Enzyme Assay |
The hypoxia/reoxygenation (H/R) model was established using the neonatal mouse cardiomyocytes (NMCMs). Different doses of PAGly were used to treat NMCMs, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Additionally, the level of cyclic adenosine monophosphate (cAMP) was examined by using a cAMP detection kit [1].
In vitro receptor binding assays for phenylacetylglycine are performed to assess its affinity for β2AR. The assay typically uses cells expressing β2AR (e.g., HEK293 cells transfected with β2AR) and measures the displacement of a radiolabeled or fluorescently labeled β2AR ligand (e.g., ¹²⁵I-cyanopindolol or fluorescent propranolol). The displacement of the labeled ligand is measured, and the IC50 or Kd is determined. Functional assays measure the activation of β2AR by assessing cAMP production using ELISA or by detecting the phosphorylation of downstream targets (e.g., PKA substrates) by Western blotting. The assay includes positive controls (known β2AR agonists such as isoproterenol) and negative controls (vehicle only). |
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: Neonatal mouse cardiomyocytes (NMCMs) Tested Concentrations: 10, 33 and 100 μM Incubation Duration: Half an hour before H/R injury Experimental Results: Inhibited disreoxygenation injury apoptosis. Western Blot Analysis[1] Cell Types: Neonatal induced mouse cardiomyocytes (NMCMs) Tested Concentrations: 10, 33 and 100 μM Incubation Duration: Half an hour before H/R injury Experimental Results: Dramatically diminished the ratio of Bax/Bcl2 and cleaved-caspase 3 expression. Enhanced p-PI3K protein expression. cAMP levels were increased in the early stage and then gradually diminished. In vitro cell-based assays for phenylacetylglycine are performed using cardiomyocytes (e.g., H9c2 or primary neonatal rat cardiomyocytes) to assess its cardioprotective effects. Cells are treated with phenylacetylglycine (typically 1-100 μM) prior to exposure to ischemia/reperfusion or other apoptotic stimuli. Cell viability is assessed using MTT or LDH release assays. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining or by detecting caspase-3/7 activity. β2AR activation is confirmed by measuring cAMP levels or PKA activity. The protective effects of phenylacetylglycine are compared to vehicle controls and positive controls (known β2AR agonists). The role of β2AR is confirmed using selective antagonists (e.g., ICI-118,551). |
| Animal Protocol |
Mouse model of myocardial I/R injury was established in C57BL/6 mice, and different doses of phenylacetic acid were administrated intraperitoneally. Apoptosis of myocardial cells was detected by TUNEL and α-actin staining. The area at risk and the infarct areas were identified by 2,3,5-triphenyltetrazolium chloride (TTC) and Evans blue staining. Western blotting was used to measure the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), total Akt (t-Akt), phosphorylated Akt (p-AKT), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3 [1].
In vivo animal studies with phenylacetylglycine are conducted in rodent models of myocardial ischemia/reperfusion injury. Mice or rats are subjected to temporary occlusion of the left anterior descending (LAD) coronary artery followed by reperfusion. Phenylacetylglycine is administered intraperitoneally or intravenously prior to or during ischemia, typically at doses ranging from 1 to 50 mg/kg. Infarct size is assessed by TTC staining, and cardiac function is assessed by echocardiography. Markers of apoptosis (TUNEL, caspase-3) and inflammation (cytokine levels, myeloperoxidase activity) are measured in cardiac tissue. The role of β2AR is confirmed using selective antagonists. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of phenylacetylglycine have not been extensively characterized. As a small molecule (molecular weight 193.20), the compound is expected to have good oral bioavailability and tissue distribution. Phenylacetylglycine is an endogenous metabolite that is produced by gut bacteria and can enter the circulation. The compound's levels in plasma and tissues are influenced by diet, gut microbiome composition, and host metabolism. Phenylacetylglycine is metabolized and excreted via the kidneys. For research use, the compound is typically dissolved in appropriate solvents (e.g., DMSO, saline) and administered in vivo.
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| Toxicity/Toxicokinetics |
Phenylacetylglycine is an endogenous metabolite and is generally considered to have low toxicity. The compound is produced by gut bacteria and is present in the circulation at physiological concentrations. No specific toxicological studies have been reported in the literature. As a research chemical, standard safety precautions should be followed when handling phenylacetylglycine. The compound is for research use only and not for human therapeutic applications. Further studies are needed to fully characterize the safety profile of phenylacetylglycine, particularly at pharmacological doses.
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| References | |
| Additional Infomation |
Phenylacetylglycine is an N-acylglycine with a phenylacetyl group replacing the nitrogen atom. It is a metabolite in both mice and humans. It is a monocarboxylic acid amide, monocarboxylic acid, and N-acylglycine. It is the conjugate acid of phenylacetylglycine (1-). Phenylacetylglycine has been reported in Homo sapiens, Trypanosoma brevicornu, and other organisms with relevant data. N-Phenylacetylglycine is a metabolite found or produced in Saccharomyces cerevisiae.
Phenylacetylglycine is a gut microbial metabolite that has emerged as a key regulator of cardiovascular function through its action on the β2 adrenergic receptor. The compound highlights the important role of the gut microbiome in modulating host physiology and disease susceptibility. The gut-heart axis has become an area of intense research, with gut microbial metabolites being implicated in various cardiovascular diseases, including heart failure, atherosclerosis, and hypertension. Phenylacetylglycine's cardioprotective effects make it a compound of interest for the development of novel therapies for ischemic heart disease. The compound is available from chemical suppliers for research purposes. |
| Molecular Formula |
C10H11NO3
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|---|---|
| Molecular Weight |
193.20
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| Exact Mass |
193.073
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| CAS # |
500-98-1
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| Related CAS # |
N-(Phenylacetyl-d5)glycine;1189920-31-7
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| PubChem CID |
68144
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| Appearance |
White to off-white solid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
476.5±38.0 °C at 760 mmHg
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| Melting Point |
144ºC
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| Flash Point |
242.0±26.8 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
0.18
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
14
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| Complexity |
209
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])N([H])C([H])([H])C(=O)O[H]
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| InChi Key |
UTYVDVLMYQPLQB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H11NO3/c12-9(11-7-10(13)14)6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H,11,12)(H,13,14)
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| Chemical Name |
2-(2-phenylacetamido)acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (517.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (4.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.1760 mL | 25.8799 mL | 51.7598 mL | |
| 5 mM | 1.0352 mL | 5.1760 mL | 10.3520 mL | |
| 10 mM | 0.5176 mL | 2.5880 mL | 5.1760 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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