Dacomitinib is a selective and irreversible inhibitor of EGFR. It is a drug candidate for the treatment of non-small cell lung carcinoma. It is current under the Phase III clinical trials. It also shows potential for the treatment of HER-2 amplified breast cancer cells lines that are resistant to trastuzumab and lapatinib.
Dacomitibib (Dacomitinib, PF299804) is an effective and irreversible pan-ErbB inhibitor that is most effective in EGFR, with an IC50 of 6 nM. It is also highly effective in NSCLCs that carries EGFR or ERBB2 mutants (against Gefitinib) and EGFR T790M mutant. Phase 2.
Dacomitinib is taken orally once-daily. It is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases. Dacomitinib targets multiple receptors of the HER pathway, whereas currently marketed HER-1 (EGFR) inhibitors for non-small cell lung cancer (NSCLC) target only one receptor in this pathway,developed by Pfizer.
ChEBI: A member of the class of quinazolines that is 7-methoxyquinazoline-4,6-diamine in which the amino group at position 4 is substituted by a 3-chloro-4-fluorophenyl group and the amino group at position 6 is substituted by an (E)-4-(piperidin
Dacomitinib has advanced to several Phase III clinical trials. The results of the first trials were disappointing, with a failure to meet the study goals, Additional Phase III trials are ongoing.
Clinical evaluation of dacomitinib is ongoing in a number of clinical trials in patients with advanced NSCLC across lines of therapies and a range of histologies and molecular subtypes, such as EGFR and KRAS status.
Additionally, there is an ongoing clinical trial evaluating dacomitinib in recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN).
PF299804 is a potent, irreversible pan-ErbB inhibitor against ErbB1, ErbB2 and ErbB4 with IC50 of 6 nM, 45.7 nM and 73.7 nM, respectively.
Dacomitinib (PF299804), which name is (E)-N-[4-(3-chloro-4-fluoroanilino)-7- methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide, is a potent, orally available, highly selective, irreversible small-molecule tyrosine kinase inhibitor (TKI) of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. It is most effective against EGFR with IC50 of 6 nM. It is highly effective against NSCLCs carrying EGFR or ERBB2 mutant (anti-Gefitinib) and EGFR T790M mutant.