| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
EGFR (epidermal growth factor receptor) kinase. PF-6274484 is a high affinity and potent covalent EGFR kinase inhibitor with a Ki of 0.14 nM. It is an irreversible covalent inhibitor that reacts with the active-site cysteine residue in the ATP-binding pocket.
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| ln Vitro |
PF-6274484 is a high affinity, irreversible covalent inhibitor of EGFR kinase with a Ki of 0.14 nM. It inhibits the autophosphorylation of wild-type EGFR in A549 cells with an IC50 of 5.8 nM and EGFRL858R/T790M in H1975 cells with an IC50 of 6.6 nM.
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| ln Vivo |
PF-6274484 is a covalent EGFR kinase inhibitor that inhibits both wild-type and mutant EGFR in tumor cells. It has potential applications in cancer research, particularly for studying EGFR-driven tumors and resistance mechanisms. Its irreversible binding provides sustained target inhibition.
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| Enzyme Assay |
EGFR kinase activity assays are performed using recombinant EGFR kinase domains (wild-type and mutant). The enzyme is incubated with a peptide substrate and [γ-32P]ATP or fluorescently labeled ATP in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT). The reaction is incubated at 30°C for 30-60 minutes. Phosphorylated substrate is quantified by scintillation counting or fluorescence polarization. PF-6274484 is serially diluted and added to the reaction mixture. Ki values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular EGFR inhibition is evaluated in cancer cell lines (A549 for wild-type EGFR, H1975 for EGFRL858R/T790M). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PF-6274484 at various concentrations for 1-24 hours. EGFR autophosphorylation is measured by Western blotting using phospho-specific antibodies (e.g., p-EGFR Y1068). Downstream signaling (p-ERK, p-AKT) is also assessed. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Each experiment includes known EGFR inhibitors as positive controls and vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using EGFR-driven tumor cell lines (e.g., A549, H1975). PF-6274484 is administered orally or intraperitoneally at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis and biochemical assays (EGFR phosphorylation, downstream signaling). Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 372.78. Formula: C18H14ClFN4O2. CAS No.: 1035638-91-5. Synonyms: PF 6274484. Target: EGFR. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a covalent EGFR kinase inhibitor, potential toxicities may include skin rash, diarrhea, and interstitial lung disease (class effects of EGFR inhibitors). Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the skin and gastrointestinal tract. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PF-6274484 is also known as PF 6274484. It is a high affinity and potent covalent EGFR kinase inhibitor with a Ki of 0.14 nM. It is an irreversible covalent inhibitor that reacts with the active-site cysteine residue. It inhibits wild-type and mutant EGFR autophosphorylation with IC50s of 5.8 and 6.6 nM. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C18H14CLFN4O2
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|---|---|
| Molecular Weight |
372.780766010284
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| Exact Mass |
372.078
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| CAS # |
1035638-91-5
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| PubChem CID |
74766099
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| Appearance |
Light yellow to orange solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
578.3±50.0 °C at 760 mmHg
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| Flash Point |
303.5±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.691
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| LogP |
3.87
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
512
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)C=C
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| InChi Key |
TUYDDIWQXWTNSW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14ClFN4O2/c1-3-17(25)24-15-7-11-14(8-16(15)26-2)21-9-22-18(11)23-10-4-5-13(20)12(19)6-10/h3-9H,1H2,2H3,(H,24,25)(H,21,22,23)
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| Chemical Name |
N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]prop-2-enamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
DMSO : ~25 mg/mL (~67.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.58 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6825 mL | 13.4127 mL | 26.8255 mL | |
| 5 mM | 0.5365 mL | 2.6825 mL | 5.3651 mL | |
| 10 mM | 0.2683 mL | 1.3413 mL | 2.6825 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.
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