文献

Background Information:

Dacomitinib (PF-00299804) is a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor currently in clinical trials. It is believed to irreversibly inhibit erbB tyrosine kinase activity through binding at the ATP site and covalent modification of nucleophilic cysteine residues in the catalytic domains of erbB family members.

Reference:

1. J. A. Engelman, et al., PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007 Dec 15;67(24):11924-32.
2. A. J. Gonzales, et al., Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, Mol Cancer Ther. 2008 Jul;7(7):1880-9.
3. P. A. Jänne, et al., Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors, Clin Cancer Res. 2011 Mar 1;17(5):1131-9. Epub 2011 Jan 10.

APIM050137: DACOMITINIB

CAS No.: 1042385-75-0 (Hydrate) 1110813-31-4 (Anhydrous).
Molecular Formula: C24H25ClFN5O2 ? H2O.
Molecular Weight: 488.
Purity: >99% (HPLC at 214 and 254 nm).
QC: HPLC-MS, 1HNMR, and Quantitative Elemental Analysis.
Solubility: In DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.