Dacomitinib

• Catalog: OFC1110813314
• CAS: 1110813-31-4
• Category: Fluorinated APIs
• Purity: >98%
• MDL Number: MFCD19443734

• IUPAC Name: (E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
• InChI: InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+
• InChI Key: LVXJQMNHJWSHET-AATRIKPKSA-N
• Isomeric SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4

• Molecular Formula: C24H25ClFN5O2
• Molecular Weight: 469.94

• XLogP3-AA: 4.4
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 469.1680809 g/mol
• Monoisotopic Mass: 469.1680809 g/mol
• Topological Polar Surface Area: 79.4Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 665

Case Study

Dacomitinib for the Treatment of EGFR-Mutated NSCLC with Brain Metastases: A Phase II Clinical Evaluation

Yu Y, et al. Lung Cancer, 2025, 207, 108710.

In a multicenter, open-label Phase II study, the experimental application of dacomitinib was evaluated in treatment-naïve non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations with multiple brain metastases. Fifteen patients, each presenting with ≥3 brain lesions (≥1 lesion >1 cm), received dacomitinib orally at 45 mg/day. The study's primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), intracranial ORR (iORR), intracranial PFS (iPFS), and adverse events. The trial demonstrated a median PFS of 16.8 months with an ORR of 93.3 % and a DCR of 100 %. Intracranial outcomes were notable, with iORR reaching 66.7 % and median iPFS of 16.6 months. Safety analyses indicated manageable grade ≥3 adverse events, confirming dacomitinib's robust systemic and intracranial efficacy in EGFR-mutated NSCLC.

In vitro Characterization of Dacomitinib Binding to Human α1-Acid Glycoprotein

Hu Z-Y, et al. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2024, 314, 124197.

Dacomitinib was investigated for its interaction with human α1-acid glycoprotein (HAG) using multispectral analysis and computational modeling. Fluorescence quenching experiments demonstrated static quenching through 1:1 complex formation, with a high binding affinity, significantly exceeding that observed with serum albumin. Thermodynamic analysis revealed hydrogen bonding and hydrophobic forces as primary stabilizers of the HAG-dacomitinib complex. Circular dichroism indicated subtle alterations in HAG secondary structure upon drug binding. Molecular docking and molecular dynamics simulations identified key amino acid residues responsible for interaction within the hydrophobic cavity of HAG. Furthermore, synergistic binding enhancement was observed in the presence of Mg²⁺ and Co²⁺ ions, which increased the stability and half-life of the drug. These findings emphasize the critical role of protein-drug binding in modulating dacomitinib's pharmacokinetics.