Dacomitinib

SKU: orb1305418

Description

Dacomitinib (PF-00299804) is a potent, orally active, and highly selective small-molecule inhibitor targeting the HER family tyrosine kinases, with IC50 values of 6 nM (EGFR), 45.7 nM (ERBB2), and 73.7 nM (ERBB4). It is widely used in preclinical research to investigate oncogenic signaling in vitro and has demonstrated antitumor efficacy in various in vivo cancer models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1110813-31-4
• MW: 469.94
• Purity: 99.34%
• Formula: C₂₄H₂₅ClFN₅O₂
• SMILES: COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)\C=C\CN1CCCCC1
• Target: EGFR,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.26 mM);DMSO:30 mg/mL (63.84 mM)

Bioactivity

• Target IC50:
  EGFR:6.0 nM|ERB4:73.7 nM|ErbB2:45.7 nM
• In Vivo:
  PF299804 inhibits EGFR signaling and induces apoptosis in the H3255 GR cell line containing the EGFR T790M mutation. It also suppresses the growth of H3255 and HCC827 cells expressing the T790M mutant. In HER2-amplified gastric cancer cells, PF299804 triggers apoptosis and G1-phase arrest, inhibiting the HER family and downstream signaling pathways, including the phosphorylation of receptors in STAT3, AKT, and extracellular signal-regulated kinase (ERK). It prevents the formation of EGFR/HER2, HER2/HER3, and HER3/HER4 heterodimeric complexes in SNU216 cells, as well as the binding of HER3 to p85α. PF299804 reduces phosphorylation levels of HER2, EGFR, HER4, AKT, and ERK in most sensitive cell lines. It exerts its anti-proliferative effect through G0/G1 phase arrest and induction of apoptosis. In a study of 47 human breast cancer and immortalized breast epithelial cell lines, PF299804 preferentially inhibited the growth of HER-2-amplified breast cancer cell lines compared to non-amplified lines (RR = 3.39, p < 0.0001).
• In Vitro:
  PF-299804 (15 mg/kg, p.o.) exhibits strong antitumor activity, inducing significant tumor regression in various human cancer xenograft models. These include models expressing and/or overexpressing members of the ERBB family, or those harboring the double mutation (L858R/T790M) in ERBB1 (EGFR), associated with resistance to erlotinib and gefitinib.
• Cell Research:
  Growth and inhibition of growth is assessed by 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. This assay, a colorimetric method fordetermining the number of viable cells, is based on the bioreduction of MTS by cells to a formazan product that is soluble in cell culture medium, can be detected spectrophotometrically. The cells are exposed totreatment for 72 hours, and the number of cells used per experiment is determined empirically. All experimental points are set up in 6 to 12 wells, and all experiments are repeated at least thrice. The data are graphically displayed using GraphPad Prism version 3.00 for Windows (GraphPad Software). The curves are fitted using a nonlinear regression model with a sigmoidal dose response.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, EGFR, Epidermal growth factor receptor, ErbB-1, Inhibitor, HER1, HER2/ErbB2, Dacomitinib, Apoptosis, PF299804, PF-299804, PF299, PF-299, PF 299, PF 299804, PF00299804, PF-00299804, PF 00299804

Compound Identifiers

PubChem CID

11511120