Dacomitinib

Dacomitinib is an irreversible small-molecule inhibitor from the EGFR/HER family, developed by Pfizer and available as a research-grade reference standard for laboratories in kinase biology and oncology drug discovery. Pfizer Dacomitinib, also known by its research code PF-00299804, belongs to the second generation of pan-HER tyrosine kinase inhibitors. Unlike reversible EGFR blockers, it forms a covalent bond with a cysteine residue in the kinase domain, keeping the target inactivated long-term. The Dacomitinib chemical structure contains a quinazoline scaffold, a 3-chloro-4-fluoroanilino substituent, and an electrophilic α,β-unsaturated amide responsible for covalent target engagement. Researchers can use the verified analytical data to confirm the Dacomitinib structure and identity of the reference material.

Application of Dacomitinib

In preclinical models, Dacomitinib has demonstrated activity against selected EGFR variants associated with resistance to first-generation inhibitors, including T790M. These findings support its use as a reference compound in studies of EGFR inhibitor resistance. 

Dacomitinib has also shown preclinical activity in selected ERBB2-mutant models, including models with reduced sensitivity to first-generation EGFR inhibitors.  

In Vitro

Biochemical assays place Dacomitinib potency at an IC50 of 6 nM against EGFR, 45.7 nM against HER2 and 73.7 nM against HER4. In HER2-amplified breast cancer lines resistant to trastuzumab and lapatinib, Dacomitinib still suppressed proliferation at submicromolar concentrations, reducing phosphorylation of HER2, EGFR, HER4, AKT and ERK, and pushing sensitive cells toward G0-G1 arrest combined with apoptosis.

In Vivo

In xenograft models bearing EGFR-mutant tumors, oral dosing produced dose-dependent inhibition of EGFR and HER2 autophosphorylation alongside measurable tumor growth suppression, including activity in intracranial models of EGFR-amplified brain tumors relevant to CNS metastasis research.

Biochemical and Physiological Actions

Dacomitinib blocks ATP binding within the EGFR, HER2 and HER4 kinase domains through covalent attachment, shutting down autophosphorylation and downstream RAS-MAPK and PI3K-AKT signaling. This explains why HER2-amplified or EGFR-mutant lines are disproportionately sensitive, while wild-type lines need higher concentrations for a comparable effect. Structural reference data, including Dacomitinib SMILES, further support compound identification and computational research applications. 

Features and Benefits of Dacomitinib

For labs building EGFR or pan-HER research panels, Dacomitinib offers:

• an irreversible, covalent binding mode that distinguishes it mechanistically from reversible EGFR inhibitors in comparative studies;
• documented activity across EGFR, HER2 and HER4, useful for pan-HER selectivity profiling;
• Dacomitinib Pfizer reference standard for research applications in kinase biology and oncology drug discovery;
• CAS 1110813-31-4 at 95% purity with NMR/LCMS-verified quality control, supplied under agreement from Pfizer Inc.

The well-characterized Dacomitinib molecular structure makes the compound suitable as a reference for kinase inhibitor profiling and structure–activity relationship studies.