| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
In RINm5f cells transfected with human GPR119 (RIN-119 cells), treatment with 10 μM PSN375963 significantly increased insulin secretion compared to stimulation with 16 mM glucose alone. In parental RINm5f cells, which do not express GPR119, PSN375963 did not increase insulin secretion, suggesting its effect on insulin release is GPR119-dependent. [2]
In MIN6c4 mouse insulinoma cells, which endogenously express GPR119, PSN375963 (3.3 μM and 10 μM) did not significantly increase glucose-stimulated insulin secretion (GSIS) in the presence of 16 mM glucose. At 10 μM in 2.8 mM glucose, a slight but significant increase in insulin secretion was observed. [2] In MIN6c4 cells, PSN375963 (3.3 μM and 10 μM) suppressed intracellular cAMP production in the presence of both 2.8 mM and 16 mM glucose. The reduction was significant at both concentrations in 2.8 mM glucose and at 10 μM in 16 mM glucose. This contrasts with its reported ability to increase cAMP in GPR119-transfected HEK293 cells, suggesting possible off-target effects in MIN6c4 cells. [2] In MIN6c4 cells, PSN375963 (3.3 μM) induced an increase in intracellular calcium [Ca²⁺]ᵢ in the presence of 2.8 mM glucose. However, it did not potentiate the [Ca²⁺]ᵢ increase induced by 16 mM glucose. [2] In MIN6c4 cells, PSN375963 (3.3 μM) did not reverse the inhibition of GSIS caused by the KATP channel opener diazoxide or the voltage-dependent calcium channel blocker nitrendipine. [2] |
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| ln Vitro |
Similar to glucagon-like peptide 1 (GLP-1) and its receptor, the endogenous ligand OEA signals through GPR119 by affecting intracellular calcium, cAMP, and insulin production [2].
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| Cell Assay |
Insulin Secretion Assay in RINm5f and RIN-119 Cells: RINm5f cells (parental or stably transfected with human GPR119) were plated and stimulated with 16 mM glucose alone or with 10 μM of PSN375963 in KRBH buffer without BSA for 2 hours. Supernatants were collected, and insulin concentration was measured using an insulin assay kit. [2]
Insulin Secretion Assay in MIN6c4 Cells: MIN6c4 cells were plated in 96-well plates and rested in KRBH buffer with 2.8 mM glucose for 30 minutes. Cells were then stimulated with various concentrations of PSN375963 (0.37, 1.1, 3.3, and 10 μM) in the presence of either 2.8 mM or 16 mM glucose for 2 hours. Supernatants were collected for insulin measurement. In some experiments, cells were pre-incubated with diazoxide (200 μM) or nitrendipine (5 μM) for 10 minutes before the addition of glucose and PSN375963 (3.3 μM). [2] cAMP Assay in MIN6c4 Cells: MIN6c4 cells in 96-well plates were incubated in KRBH with 2.8 mM glucose for 30 minutes. Cells were then treated with PSN375963 (3.3 μM or 10 μM) in the presence of either 2.8 mM or 16 mM glucose for 2 hours. cAMP levels were measured using a cAMP EIA kit and normalized to protein concentration. [2] Calcium Assay in MIN6c4 Cells: MIN6c4 cells in 384-well plates were loaded with a calcium-sensitive dye for 1 hour. After resting in KRBH with 2.8 mM glucose, cells were either maintained in 2.8 mM glucose or stimulated with 16 mM glucose. PSN375963 (3.3 μM) was then added, and changes in intracellular calcium [Ca²⁺]ᵢ were monitored continuously for up to 20 minutes using a FLIPR instrument. [2] |
| References |
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| Additional Infomation |
PSN375963 is a synthetic, commercially available compound identified as a GPR119 agonist. It has been reported to increase intracellular cAMP in a GPR119-dependent manner in HEK293 cells overexpressing the receptor. [2]
In this study using MIN6c4 cells (which endogenously express GPR119), PSN375963 showed divergent effects compared to the endogenous GPR119 ligand OEA. It did not enhance GSIS, suppressed cAMP production, and increased calcium at low glucose, suggesting it may have off-target effects that make it unsuitable as a GPR119-specific research tool in certain cellular contexts. [2] The EC50 for PSN375963 in a cAMP assay using HEK293-GPR119 cells is 13.9 μM. Its relatively low potency may contribute to its observed off-target effects. [2] |
| Exact Mass |
285.184
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|---|---|
| CAS # |
388575-52-8
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| Related CAS # |
PSN 375963 hydrochloride;1781834-82-9
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| PubChem CID |
2875918
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
440.1±47.0 °C at 760 mmHg
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| Flash Point |
209.8±23.3 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.521
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| LogP |
5.16
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
21
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| Complexity |
298
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O1C(C2CCC(CCCC)CC2)=NC(C2C=CN=CC=2)=N1
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| InChi Key |
OAVLEYPTWABFLF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H23N3O/c1-2-3-4-13-5-7-15(8-6-13)17-19-16(20-21-17)14-9-11-18-12-10-14/h9-13,15H,2-8H2,1H3
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| Chemical Name |
5-(4-butylcyclohexyl)-3-pyridin-4-yl-1,2,4-oxadiazole
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| Synonyms |
PSN375963 PSN-375963 PSN 375963
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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 : ~50 mg/mL (~175.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.76 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (8.76 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 25.0 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: ≥ 2.5 mg/mL (8.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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