658552

AG 1478

A cell-permeable, reversible, ATP-competitive, highly potent and selective inhibitor of epidermal growth factor receptor kinase versus HER2-neu and platelet-derived growth factor receptor kinase.

• Synonym(s): AG 1478, 4-(3-Chloroanilino)-6,7-dimethoxyquinazoline
• Empirical Formula (Hill Notation): C₁₆H₁₄ClN₃O₂
• CAS Number: 175178-82-2
• Molecular Weight: 315.75
• MDL number: MFCD00270914
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: pale yellow
• solubility: DMSO: 5 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• InChI: 1S/C16H14ClN3O2/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)
• InChI key: GFNNBHLJANVSQV-UHFFFAOYSA-N

Description

General description

A cell-permeable, reversible, ATP-competitive, highly potent and selective inhibitor of epidermal growth factor receptor kinase (IC₅₀ = 3 nM) versus HER2-neu (IC₅₀ >100 µM) and platelet-derived growth factor receptor kinase (IC₅₀ >100 µM). Abolishes MAP kinase (ERK) activation induced by Angiotensin II (Cat. No. 05-23-0101). Also inhibits the activation of EGFR kinase and MAP kinase by 4-hydroxynonenal. Downregulates ARF1 activity and disperses Golgi structure. A 10 mM (1 mg/317 µl) solution of AG 1478 (Cat. No. 658548) in DMSO is also available.

A cell-permeable, reversible, ATP-competitive, highly potent and specific inhibitor of the epidermal growth factor (EGF) receptor tyrosine kinase (IC₅₀ = 3 nM). Much higher concentrations are required for inhibition of the kinase activity of the closely-related HER2 (neu/erb-B2) receptor (IC₅₀ >100 µM), the platelet-derived growth factor (PDGF) receptor (IC₅₀ >100 µM), and p210^Bcr-Abl (IC₅₀ >50 µM). Its mechanism of inhibition likely mimics that of the related compound, 4-(3-chloroanilino)quinazoline (CAQ), a competitive inhibitor with respect to ATP. Downregulates ARF1 activity and disperses Golgi structure.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Epidermal growth factor receptor kinase

Product competes with ATP.

Reversible: yes

Target IC₅₀: 3 nM against epidermal growth factor receptor kinase

Warning

Toxicity: Standard Handling (A)

Preparation Note

Further dilute with aqueous buffers just prior to use.

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Pan, H., et al. 2008. J. Biol. Chem.283, In press.
Liu, W., et al. 1999. J. Cell Sci.112, 2409.
Eguchi, S., et al. 1998. J. Biol. Chem. 273, 8890.
Levitzki, A., and Gazit, A. 1995. Science267, 1782.
Fry, D.W., et al. 1994. Science265, 1093.
Osherov, N., and Levitski, A. 1994. Eur. J. Biochem.225, 1047.
Ward, W.H., et al. 1994. Biochem. Pharmacol.48, 659.

Legal Information

Sold under license of U.S. Patent 5,457,105 and European Patent 0,566,266.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3