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Purity: ≥98%
AG-1478 HCl (also known as Tyrphostin AG-1478) is a novel, potent and selective EGFR (epidermal growth factor receptor) inhibitor with IC50 of 3 nM in cell-free assays. It reversibly inhibits rat brain Kv1.5 potassium channels with IC50 of 9.8 µM which is independent of protein tyrosine kinase (PTK) activity. AG-1478 also inhibits the growth of leiomyoma and myometrium cell cultures with IC50 values of 5.6 and 5.7 µM, respectively. Previous studies suggest that EGFR antagonism may be effective for the treatment of various diseases such as cancer, angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. Therefore, AG-1478 has the potential to be used as therapeutics for these disorders.
| ln Vitro |
In chemically specified DMEM/F12 media, human lung (A549) and prostate (DU145) cancer cell lines are grown. AG-1478 (AG1478) is irreversible for growth regulation of these cell lines. Although AG-1478 is not able to totally stop the proliferation of A549 cells, it appears to be more effective at lower concentrations[1]. The angiotensin II-mediated production of TGF-β and fibronectin by cardiac fibroblasts is considerably reduced when EGFR is inhibited by the specific tyrosine kinase inhibitor AG-1478 (AG1478). AG-1478, a small-molecule inhibitor with an IC50 of 4 nM, pharmacologically inhibits EGFR[2]. Flow cytometry was used to determine how much both Polyfect (PF) and Superfect (SF) treatment boosted apoptosis in HEK 293 cells. Tempol, an antioxidant, dramatically decreased PF and SF dendrimer-mediated apoptosis. As a positive control, AG-1478 (AG1478) was utilized at a 10-fold higher dose (100 μM) than that of signaling studies, and it effectively caused apoptosis in HEK 293 cells[3].
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| ln Vivo |
In both of the obese mouse models, the administration of AG-1478 (AG1478) dramatically lowers myocardial inflammation, fibrosis, apoptosis, and dysfunction. ApoE-/- mice are given oral gavage with AG -1478 (10 mg/kg/day) or 542 (10 mg/kg/day) for 8 weeks after being fed HFD for 8 weeks (ApoE-HFD). In vivo, HFD-induced cardiac EGFR phosphorylation is blocked by AG-1478 or 542 therapy, with no impact on plasma levels of total triglycerides (TG) or low density lipoprotein (LDL)[2]. EGFR phosphorylation is robustly and consistently elevated upon administration of EGF (10 nM), and this elevation can be inhibited by the known EGFR phosphorylation inhibitor AG-1478 (AG478). Although not as much as with AG1478, increasing dosages of Polyfect (PF) significantly reduce EGF-induced EGFR phosphorylation (p<0.05)[3].
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| References |
[1]. Bojko A, et al. The effect of tyrphostins AG494 and AG1478 on the autocrine growth regulation of A549 and DU145 cells. Folia Histochem Cytobiol. 2012 Jul 5;50(2):186-95.
[2]. Li W, et al. EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice. Sci Rep. 2016 Apr 18;6:24580. [3]. Akhtar S, et al. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo. PLoS One. 2015 Jul 13;10(7):e0132215. [4]. Dorobantu CM, et al. Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6402-6. |
| Molecular Formula |
C16H15CL2N3O2
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| Molecular Weight |
352.21
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| CAS # |
170449-18-0
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| Related CAS # |
AG-1478;153436-53-4
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| SMILES |
ClC1=C([H])C([H])=C([H])C(=C1[H])N([H])C1C2=C([H])C(=C(C([H])=C2N=C([H])N=1)OC([H])([H])[H])OC([H])([H])[H].Cl[H]
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8392 mL | 14.1961 mL | 28.3922 mL | |
| 5 mM | 0.5678 mL | 2.8392 mL | 5.6784 mL | |
| 10 mM | 0.2839 mL | 1.4196 mL | 2.8392 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.
 Small molecule EGFR inhibitors attenuate HFD-induced EGFR phosphorylation and myocardial fibrosis in ApoE−/−mouse hearts.Sci Rep.2016 Apr 18;6:24580. |
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 542 or AG1478 suppress HFD-induced inflammation in ApoE−/−mouse hearts.Sci Rep.2016 Apr 18;6:24580. |
 EGFR inhibitors reverse HFD-induced hypertrophic remodeling, fibrosis and apoptosis in C57BL/6 mouse heart.Sci Rep.2016 Apr 18;6:24580. |
 EGFR inhibitors attenuate PA-induced inflammation in H9C2 Cells.Sci Rep.2016 Apr 18;6:24580. |
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 EGFR inhibitors reverse PA-induced hypertrophy, fibrosis and apoptosis in H9C2 cells.Sci Rep.2016 Apr 18;6:24580. |
 PA induces EGFR activation through TLR4/c-Src signaling cascade in H9C2 cells.Sci Rep.2016 Apr 18;6:24580. |
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