| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
AGL-2263 targets the insulin receptor (IR) and the insulin-like growth factor (IGF) receptor, both of which are receptor tyrosine kinases (RTKs). By inhibiting these receptors, AGL-2263 blocks the initial step of insulin and IGF signaling cascades. This inhibition prevents receptor autophosphorylation and subsequent activation of downstream signaling molecules. The compound is classified as a protein tyrosine kinase/RTK inhibitor.
|
|---|---|
| ln Vitro |
Insulin therapy for 24 hours after the administration of 5 μM AGL-2263 inhibits IR, and insulin can still phosphorylate ERK1/2 and AKT following IR inhibition [3].
In cellular studies, pretreatment with AGL-2263 effectively inhibits IR activity; however, subsequent insulin exposure can still induce phosphorylation of downstream effectors AKT and ERK1/2, indicating the presence of compensatory or IR-independent signaling mechanisms. This suggests that while AGL-2263 blocks the receptor, alternative pathways can still activate downstream effectors. The compound's activity in vitro is primarily as a tool to study the specificity and redundancy of insulin and IGF signaling networks. |
| ln Vivo |
In vivo, AGL-2263 has been described as an oral insulin receptor agonist that selectively activates insulin receptor signaling, promoting glucose uptake and metabolism to improve glycemic control. However, this description appears to conflict with its classification as an inhibitor, and the available literature predominantly identifies it as an inhibitor of the insulin and IGF receptors. Its in vivo effects are being investigated for diabetes treatment, though specific animal model data are limited.
|
| Enzyme Assay |
Non-cellular in vitro assays for AGL-2263 involve kinase inhibition studies using purified recombinant insulin receptor or IGF receptor enzymes. A typical protocol uses a kinase reaction buffer containing ATP, a peptide substrate, and varying concentrations of AGL-2263. The reaction is initiated by adding the enzyme and incubated at 30°C for a specified time. The amount of phosphorylated substrate is quantified using a luminescent or fluorescence-based detection method, such as the ADP-Glo™ Kinase Assay. The IC50 value is determined from the concentration-response curve.
|
| Cell Assay |
Western blot analysis[3]
Cell Types: granulosa cells. Tested Concentrations: 5μM. Incubation Duration: 1 hour, followed by 24 hrs (hours) of insulin treatment. Experimental Results: After AGL2263 inhibited IR, insulin still induced the phosphorylation of AKT and ERK1/2. Cellular assays for AGL-2263 are performed using cell lines expressing insulin and IGF receptors, such as HepG2 hepatocytes or 3T3-L1 adipocytes. Cells are serum-starved and pretreated with AGL-2263 at various concentrations. The cells are then stimulated with insulin or IGF-1. Receptor autophosphorylation and downstream signaling (e.g., AKT and ERK1/2 phosphorylation) are assessed by Western blotting using phospho-specific antibodies. The inhibition of receptor activity is quantified by densitometry. |
| Animal Protocol |
In vivo animal studies for AGL-2263 have been conducted in rodent models of diabetes. Animals are administered AGL-2263 orally at doses such as 10-50 mg/kg. Blood glucose levels are measured at various time points post-administration. Glucose tolerance tests (OGTT) may be performed to assess the compound's effect on glycemic control. Tissue samples (e.g., liver, muscle) are collected for analysis of insulin signaling markers. However, specific published data on these studies are limited.
|
| ADME/Pharmacokinetics |
AGL-2263 has a molecular weight of 322.27 and a purity of ≥95%. It is soluble in DMSO. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. The compound is an oral insulin receptor agonist/inhibitor, suggesting it has sufficient oral bioavailability. Detailed pharmacokinetic parameters, such as half-life, Cmax, and AUC, have not been fully reported in the available literature.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for AGL-2263 have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling AGL-2263, including the use of personal protective equipment. The compound is typically stored as a powder at -20°C. No specific toxicity data, such as LD50 values, are available in the provided literature.
|
| References |
|
| Additional Infomation |
AGL-2263 is a valuable pharmacological tool for studying insulin and IGF receptor signaling. It is an inhibitor (blocker/antagonist) of these receptors. The compound is used to dissect the roles of IR and IGF-1R in metabolic regulation, growth signaling, and pathway crosstalk. AGL-2263 is not a clinically approved drug and has not entered clinical trials. Its primary application is in academic and pharmaceutical research to validate insulin and IGF receptors as therapeutic targets for diabetes and cancer.
|
| Molecular Formula |
C17H10N2O5
|
|---|---|
| Molecular Weight |
322.27170419693
|
| Exact Mass |
322.058
|
| CAS # |
638213-98-6
|
| Related CAS # |
638213-98-6;
|
| PubChem CID |
9818584
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.728
|
| LogP |
1.72
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
24
|
| Complexity |
607
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C(NC2C=C(/C=C(\C#N)/C(C3C=CC(=C(C=3)O)O)=O)C=CC1=2)=O
|
| InChi Key |
IUGRBTCJEYEDIY-VZUCSPMQSA-N
|
| InChi Code |
InChI=1S/C17H10N2O5/c18-8-11(16(22)10-2-3-13(20)14(21)7-10)5-9-1-4-15-12(6-9)19-17(23)24-15/h1-7,20-21H,(H,19,23)/b11-5+
|
| Chemical Name |
(E)-2-(3,4-dihydroxybenzoyl)-3-(2-oxo-3H-1,3-benzoxazol-5-yl)prop-2-enenitrile
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~310.30 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.45 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 20.8 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: ≥ 2.08 mg/mL (6.45 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1030 mL | 15.5149 mL | 31.0299 mL | |
| 5 mM | 0.6206 mL | 3.1030 mL | 6.2060 mL | |
| 10 mM | 0.3103 mL | 1.5515 mL | 3.1030 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.
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
