1. Product Overview
Tyrphostin AG 1478 (CAS 406683-19-0) is a potent, selective, and cell-permeable inhibitor of the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase. It binds to the ATP-binding site of EGFR with an IC₅₀ of approximately 3 nM, exhibiting >100-fold selectivity over other tyrosine kinases such as ErbB2, PDGFR, and Src. AG 1478 is structurally derived from the tyrphostin (tyrosine phosphorylation inhibitor) family and is widely used to dissect EGFR-dependent signaling pathways, including MAPK/ERK, Akt, and STAT3 cascades, in cancer biology and cell signaling research.
2. Key Features and Benefits
• Ultra-High Potency: Inhibits EGFR autophosphorylation at low nanomolar concentrations (IC₅₀ ~3 nM), making it one of the most potent tyrphostins available.
• Exceptional Selectivity: Shows minimal activity against ErbB2 (IC₅₀ > 1 µM), PDGFR-β, c-Src, and other kinases, ensuring clean mechanistic studies of EGFR-specific pathways.
• Cell-Permeable: Rapidly crosses cell membranes and inhibits intracellular EGFR kinase activity within 15–30 minutes of treatment.
• Well-Characterized In Vivo: Demonstrated efficacy in xenograft tumor models (e.g., glioblastoma, breast cancer) and validated in hundreds of peer-reviewed studies.
• Multi-Pathway Inhibition: Effectively blocks EGFR-driven MAPK/ERK, PI3K/Akt, and JAK/STAT signaling, making it a comprehensive tool for studying receptor tyrosine kinase biology.
3. Major Applications
• Cancer Signaling Research: Used to inhibit EGFR phosphorylation and downstream signaling (p-ERK, p-Akt, p-STAT3) in cell lines derived from glioblastoma, breast, lung, colon, and head & neck cancers.
• Autophagy & Apoptosis Studies: Employed to investigate EGFR-mediated regulation of autophagic flux and programmed cell death in response to targeted therapy.
• Stem Cell & Development Biology: Applied in studies of EGFR role in neural stem cell differentiation, embryonic development, and tissue regeneration.
• Drug Resistance Mechanisms: Used to probe acquired resistance to EGFR inhibitors in cancer, including T790M and C797S mutation models.
• Tumor Xenograft Models: Administered via intratumoral, intraperitoneal, or oral routes in mouse models to evaluate EGFR inhibition in vivo.
4. Technical Specifications
Item Description
Product Name Tyrphostin AG 1478 (EGFR Inhibitor)
Synonyms AG-1478; NSC 693255; 4-(3-Chloro-4-fluorophenyl)amino-6-(3-morpholin-4-ylpropoxy)quinazoline; AG1478
CAS Number 406683-19-0
Molecular Formula C₂₁H₂₂ClFN₄O₂
Molecular Weight 432.88 g/mol
MDL Number MFCD03407404
Assay (Purity) ≥98% (HPLC)
Appearance Pale yellow to yellow crystalline solid or powder
Melting Point 184–186 °C (Literature)
Boiling Point ~586.5 °C (Predicted)
Density ~1.35 g/cm³ (Predicted)
pKa (Predicted) ~6.2 (Morpholine N)
logP (Predicted) ~4.5
Solubility DMSO: ≥50 mg/mL (115 mM, clear solution, sonication recommended)
Ethanol: ~10–20 mg/mL
Water: Practically insoluble (<0.1 mg/mL)
Dilute Acid: Slightly soluble as hydrochloride salt
Spectral Data ¹H NMR (DMSO‑d₆, 400 MHz): δ 2.40 (br s, 4H, morpholine CH₂), 2.55 (t, J≈6.5 Hz, 2H, OCH₂CH₂), 3.60 (t, J≈6.5 Hz, 2H, OCH₂), 3.75 (br s, 4H, morpholine CH₂), 6.80 (dd, J=8.5, 2.5 Hz, 1H, ArH), 7.15–7.35 (m, 3H, ArH), 7.55 (d, J=8.5 Hz, 1H, ArH), 8.45 (s, 1H, quinazoline H), 9.85 (br s, 1H, NH).
¹³C NMR (DMSO‑d₆):δ 44.5, 53.5, 66.5, 67.0, 110–160 (aromatic/quinazoline), 165.5 (C=N).
SMILES FC1=C(Cl)C=C(C=C1)NC2=NC=C(C=C2)OCCCN3CCOCC3
InChI Key ZQLIJIVYZUTJQE-UHFFFAOYSA-N
Storage (Powder) -20°C, protected from light and moisture; stable ≥2–3 years
Solution Stability DMSO stocks stable at -20°C for 3–6 months; avoid repeated freeze-thaw; working dilutions should be used within 24 h
HS Code 2934.99.90
5. Storage and Handling
• Powder Storage: Store sealed vial at -20°C (or -80°C for long-term), protected from light in a desiccated environment. Stable for at least 24 months from date of manufacture.
• Stock Solution: Dissolve in anhydrous DMSO to 10–20 mM (4–8 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. Protect from light.
• Working Dilution: Dilute into cell culture medium immediately before use. Final DMSO concentration in assays should not exceed 0.1% (v/v). For in vivo studies, prepare fresh suspension in vehicle (e.g., 5% DMSO + 95% corn oil or saline with 0.1% Tween-80).
• Freeze-Thaw: Aliquot DMSO stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (if long-term exposure, based on structural analogy to quinazoline derivatives — handle with caution).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P261: Avoid breathing dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P330: Rinse mouth if swallowed.
• P337+P313: If eye irritation persists: Get medical advice/attention.
• P403+P233: Store in a well-ventilated place. Keep container tightly closed.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce toxic fumes including HF, HCl, and nitrogen oxides.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood. Keep container closed when not in use. Store at -20°C, protected from light and moisture. Keep away from strong oxidizers and strong acids.
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially bioactive and suspected carcinogenic compound.
