| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
| Targets |
(E)-AG-556 targets epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that plays a critical role in cell proliferation, survival, and differentiation. EGFR is frequently overexpressed or mutated in various cancers, including non-small cell lung cancer, breast cancer, and colorectal cancer. By selectively inhibiting EGFR, (E)-AG-556 blocks receptor autophosphorylation and downstream signaling pathways such as RAS-RAF-MEK-ERK and PI3K-AKT-mTOR. The compound also blocks LPS-induced TNF-α production, demonstrating anti-inflammatory activity through modulation of inflammatory signaling pathways. Its dual EGFR inhibitory and anti-inflammatory activities make it a valuable tool for studying EGFR biology, inflammation, and for developing novel therapeutics.
|
|---|---|
| ln Vitro |
In vitro, (E)-AG-556 demonstrates highly selective inhibition of EGFR. In cell-based assays, the compound inhibits EGF-stimulated EGFR phosphorylation and downstream signaling. (E)-AG-556 also blocks LPS-induced TNF-α production in immune cells, demonstrating anti-inflammatory activity. The compound's activity is concentration-dependent, with effective concentrations typically ranging from 0.1 to 100 µM. Its dual EGFR inhibitory and anti-inflammatory activities make it a valuable tool for studying EGFR biology, inflammation, and for developing novel therapeutics for cancer and inflammatory diseases. Detailed IC50 values for EGFR inhibition are available in published literature.
|
| ln Vivo |
In vivo, (E)-AG-556 has been studied in preclinical models of cancer and inflammation. The compound's ability to inhibit EGFR and block TNF-α production may contribute to antitumor and anti-inflammatory effects. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying EGFR signaling and inflammation. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
|
| Enzyme Assay |
The in vitro EGFR inhibition assay for (E)-AG-556 typically uses purified EGFR kinase domain or immunoprecipitated EGFR from cell lysates. The assay is performed in 96-well plates with ATP, a substrate peptide, and varying concentrations of the test compound (typically 0.1 nM to 100 µM). The reaction is initiated by adding ATP and incubated at 30°C for 30-60 minutes. Phosphorylated substrate is detected using a phospho-tyrosine-specific antibody in an ELISA format or by measuring incorporation of [³³P]-ATP. IC50 values are calculated from dose-response curves using nonlinear regression. For TNF-α inhibition assays, immune cells are stimulated with LPS in the presence of the compound, and TNF-α production is measured by ELISA. Positive controls (e.g., known EGFR inhibitors, anti-inflammatory agents) and negative controls (DMSO vehicle) are included in each assay run.
|
| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., A431, MDA-MB-468) are treated with (E)-AG-556 at concentrations ranging from 0.1 to 100 µM for 1-24 hours. EGFR phosphorylation is assessed by Western blotting using phospho-specific antibodies. Cell viability is assessed using MTT or CellTiter-Glo assays. For anti-inflammatory studies, macrophages or monocytes are treated with the compound and stimulated with LPS, and TNF-α production is measured by ELISA. Cell signaling pathways (ERK, AKT, NF-κB) are assessed by Western blotting. All experiments include appropriate controls and are performed in triplicate.
|
| Animal Protocol |
For in vivo efficacy studies, mice are used in tumor models (e.g., EGFR-driven xenografts) or inflammatory models (e.g., LPS-induced endotoxemia). (E)-AG-556 is administered intraperitoneally or orally at doses ranging from 1 to 50 mg/kg. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. For inflammatory models, serum TNF-α levels are measured by ELISA, and tissue inflammation is assessed by histology. All animal procedures are conducted in accordance with institutional guidelines.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of (E)-AG-556 have been partially characterized. The compound has a molecular weight of 336.38 and a molecular formula of C20H20N2O3. Following intraperitoneal or oral administration, the compound shows moderate absorption with a Tmax of 0.5-2 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation and conjugation as major pathways. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies of (E)-AG-556 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
|
| References |
|
| Additional Infomation |
Tyrphostin B56 is a member of the tyrphostin family of tyrosine kinase inhibitors that selectively inhibits epidermal growth factor receptor kinase activity. (National Cancer Institute)
(E)-AG-556 is a highly selective EGFR inhibitor that also blocks LPS-induced TNF-α production. It is used to study EGFR signaling and inflammation. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥99%) for laboratory use only. Its dual EGFR inhibitory and anti-inflammatory activities make it a valuable tool for studying cancer biology, inflammation, and for developing novel therapeutics. |
| Molecular Formula |
C20H20N2O3
|
|---|---|
| Molecular Weight |
336.3844
|
| Exact Mass |
336.147
|
| CAS # |
133550-41-1
|
| PubChem CID |
5328775
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.247g/cm3
|
| Boiling Point |
636.1ºC at 760mmHg
|
| Flash Point |
338.5ºC
|
| Vapour Pressure |
8.95E-17mmHg at 25°C
|
| Index of Refraction |
1.638
|
| LogP |
3.534
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
25
|
| Complexity |
502
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)CCCCNC(=O)/C(=C/C2=CC(=C(C=C2)O)O)/C#N
|
| InChi Key |
GWCNJMUSWLTSCW-SFQUDFHCSA-N
|
| InChi Code |
InChI=1S/C20H20N2O3/c21-14-17(12-16-9-10-18(23)19(24)13-16)20(25)22-11-5-4-8-15-6-2-1-3-7-15/h1-3,6-7,9-10,12-13,23-24H,4-5,8,11H2,(H,22,25)/b17-12+
|
| Chemical Name |
(E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(4-phenylbutyl)prop-2-enamide
|
| 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 (~297.28 mM)
|
|---|---|
| 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 | 2.9728 mL | 14.8641 mL | 29.7283 mL | |
| 5 mM | 0.5946 mL | 2.9728 mL | 5.9457 mL | |
| 10 mM | 0.2973 mL | 1.4864 mL | 2.9728 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
