AG-1478 hydrochloride

AG-1478 hydrochloride (Tyrphostin AG-1478 hydrochloride) is a selective EGFR tyrosine kinase inhibitor with IC50 of 3 nM. AG-1478 hydrochloride has antiviral effects against HCV and encephalomyocarditis virus (EMCV).

Product information

CAS Number: 170449-18-0

Molecular Weight: 352.22

Formula: C16H15Cl2N3O2

Synonym:

Tyrphostin AG-1478 hydrochloride

NSC 693255 hydrochloride

Chemical Name: N-(3-chlorophenyl)-6, 7-dimethoxyquinazolin-4-amine hydrochloride

Smiles: Cl.COC1=CC2=C(NC3=CC(Cl)=CC=C3)N=CN=C2C=C1OC

InChiKey: WDJDYIUSDDVWKB-UHFFFAOYSA-N

InChi: InChI=1S/C16H14ClN3O2.ClH/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11;/h3-9H,1-2H3,(H,18,19,20);1H

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

AG-1478 (AG1478) is irreversible for growth regulation of human lung (A549) and prostate (DU145) cancer cell lines, cultured in chemically defined DMEM/F12 medium. AG-1478 seems to be more effective at lower concentrations, but is unable to completely inhibit growth of A549 cells. Inhibition of EGFR by specific tyrosine kinase inhibitor AG-1478 (AG1478) significantly decreases the angiotensin II-mediated synthesis of TGF-β and fibronectin by cardiac fibroblasts. EGFR is pharmacologically inhibited by small-molecule inhibitor AG-1478 with IC50 of 4 nM. Both Polyfect (PF) and Superfect (SF) treatment lead to increased apoptosis in HEK 293 cells to a similar extent as assessed by flow cytometry. The antioxidant, tempol, significantly reduced dendrimer-mediated apoptosis for both PF and SF. AG-1478 (AG1478), at a 10-fold higher dose (100 μM) than used in signaling studies, is used as a positive control and significantly induced apoptosis in HEK 293 cells.

In Vivo:

Administration of AG-1478 (AG1478) significantly reduces myocardial inflammation, fibrosis, apoptosis, and dysfunction in both two obese mouse models. ApoE-/- mice are first fed with HFD for 8 weeks (ApoE-HFD), and then administrated with AG-1478 (10 mg/kg/day) or 542 (10 mg/kg/day) for another 8 weeks by oral gavage. AG-1478 or 542 treatment blocks HFD induced cardiac EGFR phosphorylation in vivo, without affecting the plasma level of low density lipoprotein (LDL) and total triglyceride (TG). Administration of EGF (10 nM) leads to a robust and reproducible elevation in EGFR phosphorylation that can be blocked by AG-1478 (AG1478), a known inhibitor of EGFR phosphorylation. Increasing doses of Polyfect (PF) result in a significant reduction in EGF-induced EGFR phosphorylation (p<0.05) but this is to a lesser extent than observed with AG1478.

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.

Products are for research use only. Not for human use.