| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
FOXO1[1]
FOXO1-IN-3 targets FOXO1 (Forkhead box O1), a transcription factor that regulates various cellular processes, including apoptosis, metabolism, and oxidative stress responses. FOXO1 is involved in the regulation of hepatic glucose production. By inhibiting FOXO1, FOXO1-IN-3 reduces hepatic glucose production and improves insulin sensitivity. The compound is a highly selective inhibitor of FOXO1. |
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| ln Vitro |
In normal mouse primary hepatocytes, cAMP/Dexamethasone-induced G6pc and Pck1 mRNA expression is inhibited by FOXO1-IN-3 (Compound 10) (10 μM, 6 hours) [1].
In vitro, FOXO1-IN-3 is a highly selective inhibitor of FOXO1. It binds to FOXO1 and inhibits its transcriptional activity. The compound has been shown to reduce hepatic glucose production in mouse hepatocytes. FOXO1-IN-3 is an orally active compound with good bioavailability. |
| ln Vivo |
In db/db mice, blood glucose is lowered by FOXO1-IN-3 (Compound 10) (16 mg/kg, PO, twice daily for 10 days) [1]. In diabetic mice with streptozotocin-induced β-cell depletion, FOXO1-IN-3 (16 mg/kg, orally, twice daily for 7 days) and FGF21 (0.45 mg/kg) exhibit synergistic hypoglycemic effects [1]. Despite having a short half-life, FOXO1-IN-3 (1 mg/kg intravenously, 10 mg/kg orally) has considerable plasma exposure and oral bioavailability in mice [1].
In vivo, FOXO1-IN-3 reduces hepatic glucose production in mice. It improves insulin sensitivity and glucose control in db/db mice without causing weight gain. The compound is an orally active FOXO1 inhibitor. FOXO1-IN-3 has been studied in animal models of diabetes and metabolic syndrome. |
| Enzyme Assay |
In vitro assays for FOXO1-IN-3 typically involve transcriptional activity and binding studies. A standard protocol involves treating cells expressing FOXO1 with varying concentrations of FOXO1-IN-3 (typically 0.1-100 µM) and measuring FOXO1 transcriptional activity using a luciferase reporter assay. For binding studies, surface plasmon resonance or isothermal titration calorimetry is used to measure binding affinity. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
RT-PCR[1]
Cell Types: primary hepatocytes isolated from normal mice Tested Concentrations: 10 μM Incubation Duration: 6 h Experimental Results: Inhibited cAMP/Dexamethasone induced G6pc and Pck1 mRNA expression, and did not affect Foxo1 levels. In vitro cell culture experiments with FOXO1-IN-3 typically involve hepatocytes or other cell lines expressing FOXO1. Cells are cultured in appropriate media and treated with the compound at concentrations ranging from 0.1-100 µM for 24-48 hours. FOXO1 transcriptional activity, gene expression, and cell viability are measured. The compound is used to study FOXO1-mediated signaling and metabolism. |
| Animal Protocol |
In vivo animal studies with FOXO1-IN-3 are conducted in diabetic mouse models. A typical protocol involves administering the compound orally to db/db mice at doses ranging from 1-50 mg/kg daily for 2-4 weeks. Blood glucose levels, insulin sensitivity, and body weight are monitored. Hepatic glucose production is measured.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of FOXO1-IN-3 are consistent with an orally active compound. It has good oral bioavailability and is metabolized in the liver. The compound is eliminated via hepatic and renal routes. No formal pharmacokinetic studies have been published.
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| Toxicity/Toxicokinetics |
FOXO1-IN-3 may cause skin and eye irritation. Standard laboratory safety precautions should be followed when handling this compound, including the use of gloves, safety glasses, and working in a fume hood. The compound should be stored in a cool, dry place away from light and moisture.
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| References | |
| Additional Infomation |
FOXO1-IN-3 is a highly selective, orally active inhibitor of FOXO1. It reduces hepatic glucose production and improves insulin sensitivity and glucose regulation in db/db mice without causing weight gain. It has not undergone clinical trials and is not approved as a pharmaceutical.
|
| Molecular Formula |
C22H23N7O
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|---|---|
| Molecular Weight |
401.464323282242
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| Exact Mass |
401.196
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| CAS # |
2451093-95-9
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| PubChem CID |
153524804
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| Appearance |
Off-white to yellow solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
588
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC(=C3)C4=NC5=CC=CC=C5N4
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| InChi Key |
OYUAMDGBOAEJOY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N7O/c1-28-10-12-29(13-11-28)16-8-6-15(7-9-16)22(30)25-20-14-19(26-27-20)21-23-17-4-2-3-5-18(17)24-21/h2-9,14H,10-13H2,1H3,(H,23,24)(H2,25,26,27,30)
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| Chemical Name |
N-[5-(1H-benzimidazol-2-yl)-1H-pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4909 mL | 12.4545 mL | 24.9091 mL | |
| 5 mM | 0.4982 mL | 2.4909 mL | 4.9818 mL | |
| 10 mM | 0.2491 mL | 1.2455 mL | 2.4909 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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