| Size | Price | Stock | Qty |
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| Other Sizes |
| Targets |
22 μM (FoxO1 transcriptional activity)[1]
Forkhead transcription factor forkhead box O1 (FoxO1). JY-2 is a moderately selective and orally active inhibitor of FoxO1. FoxO1 is a transcription factor that plays a key role in regulating various cellular processes, including gluconeogenesis, insulin signaling, cell cycle, and apoptosis. By inhibiting FoxO1, JY-2 modulates the expression of its target genes, thereby affecting these processes. |
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| ln Vitro |
In HepG2 and INS-1 cells, JY-2 (10-100 μM; 24 h) lessens the lipotoxicity caused by palmitic acid (PA; HY-N0830) [1].
In vitro, JY-2 inhibits FoxO1 transcriptional activity with an IC50 of 22 μM. It shows moderate inhibitory activity against FoxO3a and FoxO4. Its activity can be assessed using a cell-based reporter assay, where cells are transfected with a FoxO-responsive luciferase reporter and treated with varying concentrations of JY-2. |
| ln Vivo |
Mice treated with JY-2 (50-200 mg/kg; oral; three times for two days or daily for four weeks) do not exhibit diabetic effects[1]. The JY-2 pharmacokinetic parameters are as follows: parameters iv (20 mg/kg) po (50 mg/kg) AUCall (ng·h/mL) 5017 ± 1038 12270 ± 2775 AUCinf.obs (ng·h/mL) 5030 ± 1037 12400 ± 2753 Cmax (ng/mL) 10790 ± 3269 6826 ± 2342 Tmax (h) 0.1 ± 0.1 0.8 ± 0.7 T1/2 (h) 0.8 ± 0.2 1.3 ± 0.4 MRTinf.obs (h) 0.7 ± 0.1 2.0 ± 0. 1 F (%) 97.8
In vivo, JY-2 has shown antidiabetic activity. It is used in research to study the role of FoxO1 in disease. Specific in vivo studies have been conducted but are not detailed in the available information. |
| Enzyme Assay |
The in vitro activity of JY-2 is assessed using a cell-based FoxO1 transcriptional activity assay. Cells are co-transfected with a FoxO1 expression plasmid and a FoxO-responsive luciferase reporter plasmid. The cells are then treated with JY-2, and luciferase activity is measured to determine the IC50.
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| Cell Assay |
Real Time qPCR[1]
Cell Types: HepG2 and INS-1 cells Tested Concentrations: 10, 50 and 100 μM Incubation Duration: 24 h Experimental Results: diminished palmitic acid (PA)-induced G6Pase and PEPCK mRNA expression. Inhibited PA-induced lipid accumulation . diminished PA-induced mRNA expression of ER stress markers (ATF3, CHOP and GRP78). Western Blot Analysis[1] Cell Types: HepG2 cells Tested Concentrations: 10, 50 and 100 μM Incubation Duration: 4 h; in the presence of PA ( 500μM) Experimental Results: Increased p-FoxO1 levels in the whole cell lysate with a concurrent reduction in nuclear FoxO1 levels. To study its cellular effects, cell lines relevant to diabetes or other diseases are treated with JY-2. The expression of FoxO1 target genes, such as those involved in gluconeogenesis, is measured by qPCR. The effect on cell proliferation, apoptosis, and insulin signaling is assessed using standard assays. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice[1]
Doses: 50, 100, 200 mg/kg Route of Administration: po (oral gavage) three times for two days (9:00 AM, 7:00 PM, 9:00 AM on the next day) Experimental Results: Improved glucose tolerance. Dramatically decreased the expression of G6Pase and PEPCK mRNA in the liver. Enhanced mRNA expression of insulin and PDX-1 in the pancreas. Animal/Disease Models: db/db mice and C57BL/6J mice, high fat-diet-induced obese diabetic (DIO) model[1] Doses: 50, 100 mg/kg Route of Administration: po (oral gavage) one time/day for 4 weeks Experimental Results: diminished the levels of fasting blood glucose, improved glucose tolerance. The expression of ColIV, a fibrosis marker, was also lowered. Animal/Disease Models: C57BL/6J mice[1] Doses: 20 mg/kg or 50 mg/kg Route of Administration: IV or PO (pharmacokinetic/PK Analysis) Experimental Results: demonstrated an overall good pharmacokinetic/PK profile. The in vivo efficacy of JY-2 is evaluated in mouse models of diabetes or other diseases. The compound is administered orally. Blood glucose levels, insulin sensitivity, and other relevant parameters are measured. |
| ADME/Pharmacokinetics |
JY-2 has a molecular weight of 292.12 g/mol and a molecular formula of C13H7Cl2N3O. It is a small, orally active molecule. It is soluble in DMSO. Specific pharmacokinetic data are not widely published.
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| Toxicity/Toxicokinetics |
Specific toxicological data for JY-2 are not detailed, as it is a research compound. It is not intended for human or veterinary use. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
JY-2 is a research compound used to study the role of FoxO1 in various diseases, including diabetes and psoriasis. It is a valuable tool for investigating the FoxO1 signaling pathway and for validating FoxO1 as a potential therapeutic target. It is not an approved drug.
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| Molecular Formula |
C13H7CL2N3O
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|---|---|
| Molecular Weight |
292.12
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| Exact Mass |
290.996
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| CAS # |
339103-05-8
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| PubChem CID |
702923
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
457.4±55.0 °C at 760 mmHg
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| Flash Point |
230.4±31.5 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.613
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| LogP |
4.02
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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 |
2
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| Heavy Atom Count |
19
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| Complexity |
308
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=NC(=C1)C2=NOC(=N2)C3=C(C=C(C=C3)Cl)Cl
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| InChi Key |
WBMHQMQALJDGHI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H7Cl2N3O/c14-8-4-5-9(10(15)7-8)13-17-12(18-19-13)11-3-1-2-6-16-11/h1-7H
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| Chemical Name |
5-(2,4-dichlorophenyl)-3-pyridin-2-yl-1,2,4-oxadiazole
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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: 125 mg/mL (427.91 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4233 mL | 17.1163 mL | 34.2325 mL | |
| 5 mM | 0.6847 mL | 3.4233 mL | 6.8465 mL | |
| 10 mM | 0.3423 mL | 1.7116 mL | 3.4233 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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