| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary reported target of PEN is GPR83, a class A orphan GPCR highly expressed in the cerebellum, hippocampus, amygdala, spleen, and thymus. PEN has been suggested to act as a selective, high-affinity endogenous ligand for GPR83, with potential to regulate food intake, anxiety-like behavior, and immune responses. However, conflicting reports exist regarding PEN's ability to bind and activate GPR83, and some studies find no experimental evidence supporting PEN as a GPR83 ligand.
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| ln Vitro |
In Neuro2A cells expressing GPR83, PEN has been reported to bind to and activate GPR83 in a GTPgammaS binding assay. PEN treatment also affects behaviors including locomotion, drinking, and grooming in rats. However, a later study using multiple second messenger and GPCR activation assays, radioligand binding assays, and multiple GPR83 plasmids and PEN peptides from different sources found no experimental evidence to support PEN as a GPR83 ligand, questioning its previously assigned role.
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| ln Vivo |
ProSAAS knockout mice (which lack PEN and other proSAAS-derived peptides) display robust anxiety-like behaviors in open field, light-dark emergence, and elevated zero maze tests, suggesting that proSAAS-derived peptides including PEN play a role in emotional regulation. In rats, both PEN and bigLEN (another proSAAS-derived peptide) affect feeding, locomotion, drinking, and grooming, but the specific contribution of PEN vs. other proSAAS products is unclear.
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| Enzyme Assay |
Radioligand binding assays are performed using membranes from cells (e.g., Neuro2A or HEK293) expressing recombinant GPR83. Membranes are incubated with radiolabeled PEN (e.g., ¹2⁵I-PEN) and increasing concentrations (1 pM to 10 uM) of unlabeled PEN in binding buffer (50 mM HEPES, pH 7.4, 5 mM MgCl2, 1 mM CaCl2, 0.2% BSA) at room temperature for 60 min. Nonspecific binding is determined in the presence of 10 uM unlabeled PEN. Bound radioligand is separated by filtration through GF/B filters and counted by gamma counter. Data are fitted to a one-site binding model to calculate Kd values.
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| Cell Assay |
Functional activation assays are performed in cells expressing GPR83 using second messenger readouts. For cAMP measurement, cells are incubated with forskolin (5 uM) and various concentrations (1 nM to 10 uM) of PEN in assay buffer for 30 min at 37degC. Intracellular cAMP levels are quantified using a competitive ELISA or HTRF kit. For calcium mobilization assays, cells loaded with calcium-sensitive dye (e.g., Fluo-4) are stimulated with PEN, and fluorescence (ex/em = 494/516 nm) is measured. For GTPgammaS binding, membrane preparations are incubated with [3⁵S]GTPgammaS and PEN, then filtered and counted. Cells are also studied in 6- or 96-well plates for gene expression studies (qPCR for c-fos).
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| Animal Protocol |
ProSAAS knockout mice (generated by homologous recombination) are studied at 8-12 weeks of age. Anxiety-like behavior is assessed in the open field test (total distance traveled, time spent in center vs. periphery), light-dark emergence test, and elevated zero maze test. For feeding behavior studies, mice or rats are fasted overnight, then administered PEN (or control) via intracerebroventricular (ICV) injection (typically 1-10 nmol) and food and water intake is measured at multiple time points (1, 2, 4, 6, 12, 24 hours). Locomotor activity is monitored using automated activity chambers.
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| ADME/Pharmacokinetics |
Detailed PK data for PEN are not available. As an endogenous neuropeptide of 22 amino acids, PEN is expected to have a very short half-life (<10 min) in the bloodstream due to rapid degradation by peptidases. When administered ICV (the standard route for behavioral studies), the effective concentration in brain interstitial fluid is likely in the low nM range. The compound is rapidly cleared from CSF via bulk flow and enzymatic degradation. The TFA salt provides water solubility.
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| Toxicity/Toxicokinetics |
No specific toxicity data for PEN are reported. Given that PEN is an endogenous peptide, it is expected to have low toxicity. In proSAAS knockout mice, no overt developmental or baseline health deficits are reported, though they do display anxiety-like behaviors. At the doses used in ICV studies (1-10 nmol), no adverse neurological or behavioral effects beyond the intended target-mediated ones are observed.
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| References |
[1]. Jonathan H Wardman , et al. ProSAAS-derived Peptides Are Colocalized With Neuropeptide Y and Function as Neuropeptides in the Regulation of Food Intake. PLoS One. 2011;6(12):e28152.
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| Additional Infomation |
The physiological role of PEN and its receptor GPR83 remains an area of active investigation and debate. One study (2016) identified GPR83 as the PEN receptor, but a later study (2023) was unable to replicate these findings. This discrepancy highlights the need for further research and careful interpretation when using PEN as a GPR83 ligand. PEN is a research-grade peptide and has no approved therapeutic indications. The TFA salt form is standard for biochemical research.
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| Molecular Formula |
C104H170F3N27O36
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| Related CAS # |
PEN(mouse);1236955-25-1
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| Appearance |
Typically exists as solid at room temperature
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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) |
H2O :~100 mg/mL (~41.13 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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