AG-1478

Catalog No.S2728 Batch:S272801

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Technical Data

Formula

C16H14ClN3O2
Molecular Weight 315.75 CAS No. 153436-53-4,175178-82-2
Solubility (25°C)* In vitro DMSO 25 mg/mL (79.17 mM)
Ethanol 13 mg/mL (41.17 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO Corn oil
2.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description AG-1478 is a selective EGFR inhibitor with IC50 of 3 nM in cell-free assays, almost no activity on HER2-Neu, PDGFR, Trk, Bcr-Abl and InsR. AG-1478 (Tyrphostin AG-1478) inhibits encephalomyocarditis virus (EMCV) and hepatitis c virus (HCV) by targeting phosphatidylinositol 4-kinase IIIα (PI4KA).
Targets
EGFR [1]
(Cell-free assay)
3 nM
In vitro

AG-1478 is high selective over ErbB2 and PDGFR with IC50 of >100 μM. [1] AG-1478 preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. AG-1478 also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. [2] AG-1478 (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. [3] AG-1478 inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. [6] AG1478 is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2. [7]
In vivo

Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of AG-1478 significantly enhance the efficacy of cytotoxic drugs, with the combination of AG-1478 displaying synergistic antitumor activity against human glioma xenografts. The combination of AG-1478 and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. [4] The combination of AG-1478 (0.4 mg) with a single dose of 25 μCi 90Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone. [5]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    U87MG

  • Concentrations

    Dissolved in DMSO, final concentrations ~100 μM

  • Incubation Time

    72 hours

  • Method

    Cells are exposed to different concentrations of AG-1478 for 72 hours in 96-well plates. The effects of AG-1478 on cell growth are examined using an Alamar Blue assay. A 20-μL aliquot of Alamar Blue is added to each well, and its absorbance is determined using a Spectromax Scanning Micro plate Reader. The effects of AG-1478 are expressed as percentage of growth inhibition using untreated cells as the control (0% inhibition). Cellular DNA synthesis is determined using a [3H]thymidine incorporation assay.
Animal Study:

[4]
  • Animal Models

    Female BALB/c nu/nu mice inoculated s.c. with A431 or U87MG.Δ2-7 tumor cells

  • Dosages

    ~1 mg/kg

  • Administration

    Injection i.p. three times per week

Customer Product Validation

Data from [Data independently produced by Biomed Pharmacother, 2014, 10.1016/j.biopha.2014.09.003]

Data from [Data independently produced by Toxicol Lett, 2014, 226(1), 81-9]

Data from [Data independently produced by , , PLoS One, 2013, 8(8): e70353]

Selleck's AG-1478 has been cited by 97 publications

Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs [ Biomed Pharmacother, 2024, 180:117523] PubMed: 39405910
Calpain-2 mediates SARS-CoV-2 entry via regulating ACE2 levels [ mBio, 2024, e0228723.] PubMed: 38349185
AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling [ Cells, 2024, 13(20)1733] PubMed: 39451251
Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists [ iScience, 2024, 27(2):108839] PubMed: 38303712
Transforming Growth Factor α Evokes Aromatase Expression in Gastric Parietal Cells during Rat Postnatal Development [ Int J Mol Sci, 2024, 25(4)2119] PubMed: 38396796
Crosstalk between cancer cells and macrophages promotes OSCC cell migration and invasion through a CXCL1/EGF positive feedback loop [ Discov Oncol, 2024, 15(1):145] PubMed: 38713320
Protocol for identifying properties of ERBB receptor antagonists using the barcoded ERBBprofiler assay [ STAR Protoc, 2024, 5(2):102987] PubMed: 38635397
Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish [ JCI Insight, 2023, 8(1)e163929] PubMed: 36625346
Revitalizing Skin Repair: Unveiling the Healing Power of Livisin, a Natural Peptide Calcium Mimetic [ Toxins (Basel), 2023, 16(1)21] PubMed: 38251238
Argininosuccinate lyase drives activation of mutant TERT promoter in glioblastomas [ Mol Cell, 2022, 82(20):3919-3931.e7] PubMed: 36270249

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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