| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
(E/Z)-AG490 targets multiple tyrosine kinases including EGFR, STAT3, and JAK2/3. The active (E)-isomer inhibits EGFR, a receptor tyrosine kinase that plays a critical role in cell proliferation and survival, and is frequently overexpressed or mutated in various cancers. The compound also inhibits STAT3, a transcription factor that is activated by JAK kinases and plays a critical role in cell proliferation, survival, and immune regulation. STAT3 is constitutively activated in many cancers and contributes to tumor growth, metastasis, and resistance to therapy. (E/Z)-AG490 also inhibits JAK2 and JAK3, members of the JAK family of non-receptor tyrosine kinases that are essential for cytokine signaling. By inhibiting these targets, (E/Z)-AG490 blocks multiple signaling pathways that are critical for cell proliferation, survival, and immune function. The racemic mixture contains both the active (E)-isomer and the less active (Z)-isomer, and is commonly used as a research tool for studying JAK/STAT signaling.
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|---|---|
| ln Vitro |
In vitro, (E/Z)-AG490 demonstrates potent inhibition of EGFR, STAT3, and JAK2/3 signaling. The compound effectively inhibits EGFR autophosphorylation and downstream signaling at concentrations in the low micromolar range. (E/Z)-AG490 inhibits STAT3 phosphorylation (p-STAT3) and activation in various cell lines, leading to reduced expression of STAT3 target genes involved in cell proliferation and survival. The compound inhibits JAK2/3-mediated STAT phosphorylation in cytokine-stimulated cells. (E/Z)-AG490 has been shown to inhibit the proliferation of various cancer cell lines and to induce apoptosis in STAT3-dependent cancer cells. The compound has been used extensively to study the role of JAK/STAT signaling in cancer, inflammation, and immune regulation. The racemic mixture is commonly used in research, though the (E)-isomer is the more active form.
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| ln Vivo |
In vivo, (E/Z)-AG490 has been used in preclinical models to study the role of JAK/STAT signaling in various diseases. In mouse models of cancer, administration of (E/Z)-AG490 (typically at doses of 5-50 mg/kg via intraperitoneal injection) results in inhibition of tumor growth and induction of apoptosis in STAT3-dependent tumors. The compound has also been used in models of inflammation and autoimmune diseases, where it reduces inflammatory responses and disease severity. (E/Z)-AG490 inhibits STAT3 phosphorylation in target tissues, confirming target engagement and pathway inhibition. The compound is well-tolerated in these models at therapeutic doses, though its use is limited by its relatively modest potency and lack of selectivity. Despite these limitations, (E/Z)-AG490 has been a valuable tool for validating JAK/STAT as a therapeutic target and for generating proof-of-concept data for the development of more selective JAK/STAT inhibitors.
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| Enzyme Assay |
The inhibitory activity of (E/Z)-AG490 against EGFR, STAT3, and JAK2/3 is assessed using biochemical and cellular assays. In biochemical assays, recombinant kinases are incubated with varying concentrations of (E/Z)-AG490 (0.1-100 μM) and a peptide substrate in the presence of ATP. The kinase reaction is carried out at 30°C for 30-60 minutes, and the transfer of phosphate to the substrate is quantified using either radioactive (³³P-ATP) or fluorescence-based detection methods. IC50 values are calculated from dose-response curves. In cellular assays, EGFR phosphorylation, STAT3 phosphorylation (p-STAT3), and JAK-mediated STAT phosphorylation are measured by Western blot or ELISA after treatment with (E/Z)-AG490. IC50 values for inhibition of phosphorylation are calculated from dose-response curves.
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| Cell Assay |
Cellular activity of (E/Z)-AG490 is evaluated in various cancer cell lines and primary cells. Cells are seeded in 96-well plates and treated with (E/Z)-AG490 at concentrations ranging from 0.1 to 100 μM for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays, and IC50 values are calculated. STAT3 phosphorylation (p-STAT3) is measured by Western blot or ELISA after 1-6 hours of treatment. EGFR phosphorylation is measured by Western blot. Apoptosis is assessed by caspase-3/7 activity and annexin V/PI staining. Cell cycle analysis is performed by flow cytometry. The compound's effect on JAK/STAT signaling is confirmed by measuring the expression of STAT target genes by qRT-PCR.
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| Animal Protocol |
In animal studies, (E/Z)-AG490 is administered to rodents via intraperitoneal injection at doses of 5, 10, 25, or 50 mg/kg, once daily, for 7-28 days. In models of cancer (e.g., xenograft models), tumor volume is measured twice weekly with calipers, and tumor growth inhibition is calculated. In models of inflammation, disease severity is assessed by clinical scores, histopathology, and inflammatory markers. STAT3 phosphorylation is measured in tumor or target tissues by Western blot or IHC to confirm target engagement. Blood and plasma are collected for pharmacokinetic analysis. Pharmacodynamic biomarkers are measured in plasma or tissue to confirm pathway modulation.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Tyrosine kinase inhibitors B42: Known human metabolites include tyrosine kinase inhibitors B42, 4-O-glucuronide, and tyrosine kinase inhibitors B42, 3-O-glucuronide. Pharmacokinetic studies of (E/Z)-AG490 in rodents indicate that the compound has moderate bioavailability and a short half-life, requiring frequent dosing in preclinical studies. Following intraperitoneal administration at 10-50 mg/kg, the compound achieves peak plasma concentrations (Cmax) within 0.5-2 hours (Tmax) and has a plasma half-life of 1-3 hours. The compound shows moderate plasma protein binding and distributes to tissues including tumor tissue. Metabolism is primarily via CYP450 enzymes, and the compound is excreted in feces and urine. The relatively short half-life of (E/Z)-AG490 limits its utility in vivo, and researchers often use multiple daily doses to maintain effective concentrations. |
| Toxicity/Toxicokinetics |
Toxicology studies of (E/Z)-AG490 are limited as the compound is a research tool. In short-term (7-14 day) rodent studies at doses up to 50 mg/kg/day, the compound is generally well-tolerated with no significant adverse effects on body weight, food consumption, or general health. No significant hematological abnormalities or histopathological changes have been reported at therapeutic doses. The compound is not intended for human use and has not been evaluated in clinical trials. Researchers should follow standard safety precautions when handling the compound.
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| Additional Infomation |
Tyrphostin B42 is a monocarboxylic acid amide formed by the condensation of the carboxyl group of (2E)-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enoic acid with the amino group of benzylamine. It possesses a variety of activities, including as an EC 2.7.10.2 (non-specific protein tyrosine kinase) inhibitor, antioxidant, STAT3 inhibitor, anti-inflammatory agent, apoptosis inducer, and anti-aging agent. It is an enamide, monocarboxylic acid amide, nitrile compound, catechol compound, and secondary amide. Tyrphostin B42 belongs to the tyrosine kinase inhibitor family and can inhibit epidermal growth factor receptors, blocking the growth of leukemia cells in vitro and in vivo by inducing programmed cell death. It also inhibits constitutive activation of STAT-3 DNA binding and IL-2-induced growth of mycosis fungoides tumor cells. (National Cancer Institute)
(E/Z)-AG490 is one of the most widely used research tools for studying JAK/STAT signaling and has been cited in thousands of scientific publications. The compound has been instrumental in elucidating the role of STAT3 in cancer, inflammation, and immune regulation, and has provided proof-of-concept data for the development of more selective JAK/STAT inhibitors. Despite its limitations—including modest potency, lack of selectivity, and short half-life—(E/Z)-AG490 remains a valuable tool for mechanistic studies and for generating hypotheses about the role of JAK/STAT signaling in various biological contexts. The compound is available from commercial suppliers for research purposes and continues to be used in laboratories worldwide. The development of more selective and potent JAK/STAT inhibitors, such as ruxolitinib, tofacitinib, and others, has built upon the foundation laid by studies using (E/Z)-AG490. |
| Molecular Formula |
C17H14N2O3
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|---|---|
| Molecular Weight |
294.305
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| Exact Mass |
294.1
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| CAS # |
134036-52-5
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| Related CAS # |
AG490;133550-30-8
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| PubChem CID |
5328779
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| Appearance |
Yellow to brown solid powder
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| Density |
1.337g/cm3
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| Boiling Point |
615.2ºC at 760mmHg
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| Melting Point |
215ºC
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| Flash Point |
325.9ºC
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| LogP |
2.712
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
460
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)CNC(=O)/C(=C/C2=CC(=C(C=C2)O)O)/C#N
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| InChi Key |
TUCIOBMMDDOEMM-RIYZIHGNSA-N
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| InChi Code |
InChI=1S/C17H14N2O3/c18-10-14(8-13-6-7-15(20)16(21)9-13)17(22)19-11-12-4-2-1-3-5-12/h1-9,20-21H,11H2,(H,19,22)/b14-8+
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| Chemical Name |
(E)-N-benzyl-2-cyano-3-(3,4-dihydroxyphenyl)prop-2-enamide
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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 : ~100 mg/mL (~339.79 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.49 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 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 (8.49 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3978 mL | 16.9889 mL | 33.9778 mL | |
| 5 mM | 0.6796 mL | 3.3978 mL | 6.7956 mL | |
| 10 mM | 0.3398 mL | 1.6989 mL | 3.3978 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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