1. JAK/STAT Signaling
    Protein Tyrosine Kinase/RTK
    Stem Cell/Wnt
    Autophagy
  2. EGFR
    STAT
    Autophagy

AG-490 (Synonyms: Tyrphostin AG 490)

Cat. No.: HY-12000 Purity: 98.86%
Data Sheet SDS Handling Instructions

AG-490 is an tyrosine kinase inhibitor, inhibits EGFR and Stat-3.

For research use only. We do not sell to patients.
AG-490 Chemical Structure

AG-490 Chemical Structure

CAS No. : 133550-30-8

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10 mM * 1 mL in DMSO USD 66 In-stock
10 mg USD 60 In-stock
50 mg USD 106 In-stock
100 mg USD 138 In-stock
200 mg USD 240 In-stock
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Customer Review

    AG-490 purchased from MCE. Usage Cited in: Oncogene. 2017 May 25;36(21):2946-2956.

    (a) Immunoblotting analysis of pSTAT3, CITED4, and CCND1 in CL1-5 cells treated with AG490 (5 μM) for the indicated times. α-Tubulin is assessed as an internal control. (b) Q-PCR analysis of CITED4 in A549 cells treated with AG490 (5 μM) for the indicated times.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AG-490 is an tyrosine kinase inhibitor, inhibits EGFR and Stat-3.

    IC50 & Target

    EGFR and Stat-3[1]

    In Vitro

    AG490 inhibits the activation of Stat-3 by selectively blocking JAK2. AG490 is used to selectively inhibit JAK/Stat-3 activation. At a dose of 10 μM, Stat-3 phosphorylation is decreased by >95% and cell viability is maintained. AG490 at a dose of 10 μM results in >95% decrease in pStat-3 in EGF-stimulated A431 cells with no effect on Stat-3 mass[1]. AG-490 is a potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their cellular consequences. AG-490 abolishes IL-2-inducible [3H]thymidine incorporation in a dose-dependent manner, displaying an IC50 of 25 μM. AG-490 potently inhibits IL-2-mediated proliferation in T cells, results distinct from previous studies that showed this agent induced apoptosis in ALL cells while exerting apparently no effects on the growth of mitogen-stimulated normal T cells[2].

    In Vivo

    AG490 significantly inhibits the development of type 1 diabetes (T1D) (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 (1 mg/mouse) markedly results in disease remission in treated animals (n=23) in comparision to the absolute inability (0%; 0/10, p=0.003, Log-rank test) of DMSO and sustained eugluycemia is maintained for several months following drug withdrawal[3]. AG490 (1-10 µg) significantly attenuates ʎ-carrageenan-induced thermal hyperalgesia in a dose-dependent manner. AG490 also reduces mechanical hyperalgesia[4].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 3.3979 mL 16.9895 mL 33.9789 mL
    5 mM 0.6796 mL 3.3979 mL 6.7958 mL
    10 mM 0.3398 mL 1.6989 mL 3.3979 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    AG490 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

    A colorimetric cell proliferation assay is performed using the CellTiter 96 kit. Briefly, A431 cells are plated in 96-well plates (2000 cells/well) and cultured in DMEM/HAM's F-12 supplemented with 10% FCS for 24 h. Cells are incubated in serum-free media for 24 h. EGF (10 ng/mL) is added to all wells. Tyrphostin AG1478 (0.25 mM) and AG490 (10 mM) are added alone or in combination and the culture is incubated for the appropriate time. Medium is aspirated and CellTiter 96 Aqueous One Solution Reagent (20 μL) is added to each well. The plates are incubated at 37°C for up to 1 h and absorbance recorded at 490 nm using a 96-well plate reader. Data are derived from at least three independent experiments (in triplicate) for the both single agents and combination studies. IC50 values for Tyrphostin AG1478 (EGFR inhibitor) and AG490 (JAK/STAT inhibitor) are determined. The growth inhibitory effects of the combination are quantified using the Calucsyn software program[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3][4]

    AG490 is dissolved in sterile DMSO and brought to final volume by sterile PBS followed by several pipetting to bring the compound into solution (Mice)[3].
    AG490 is dissolved in 3.5% DMSO prior to the start of an experiment on each study (Rats)[4].

    Mice[3]
    Female NOD/LtJ, NOD.Scid, and BALB/c mice are used. One vial of compound containing 5 mg of AG490 is injected into5 mice (1 mg/mouse) via the i.p route. The control groups are receive the same volume of the vehicle under the same regimens and conditions.
    Rats[4]
    A total of 28 Male Sprague-Dawley rats (250-300 g) are used. The experiments are performed in rats 48 h after ʎ-carrageenan injection. A total of 4 groups (n=6) of rats are randomly included in the dose-response study. Group 1 is the vehicle control, which receive 100 µL i.pl. injection of 3.5% DMSO in saline. Groups 2-4 are injected with 3 different doses of AG490 (1, 5 or 10 µg). To study the effects of naloxone on AG490-induced antinociception, an additional group of rats (group 5; n=4) is observed. Group 5 is co-administered with AG490 (10 µg) and Naloxone (10 µg). The drugs are administered i.pl. in a volume of 100 µl. As reported earlier, the in vivo pharmacological effects of AG490 are observed 4 h after treatment. Thus, the behavioral tests are performed before (baseline assessment) and 4 h after treatment. First, the rats are subjected to the thermal hyperalgesia test; 10 min later, the paw pressure test is performed on the same set of rats. All the experiments are performed between 8:00 a.m. and 2:00 p.m. to reduce the confounding influence of diurnal variations, and all the procedures are performed in a blinded fashion. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    294.3

    Formula

    C₁₇H₁₄N₂O₃

    CAS No.

    133550-30-8

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥57mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 98.86%

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    Inquiry Information

    Product Name:
    AG-490
    Cat. No.:
    HY-12000
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