Dacomitinib (PF299804, PF299)


Dacomitinib (PF299804, PF299)化学構造


Dacomitinib (PF299804, PF299)は一種の有効で、不可逆的なパン(pan)ErbB阻害剤で、EGFRに作用する効果が一番強くて、無細胞試験でこのIC50値が6 nMです。Dacomitinib (PF299804, PF299)は EGFR或いはERBB2の突然変異型(耐Gefitinib)とEGFR T790M突然変異型を持っているNSCLCsに有効に作用します。臨床2期。

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  • J Immunol 2014 192(2), 722-31. Dacomitinib (PF299804, PF299) purchased from Selleck.

    J Immunol 2014 192(2), 722-31. Dacomitinib (PF299804, PF299) purchased from Selleck.

  • J Immunol 2014 192(2), 722-31. Dacomitinib (PF299804, PF299) purchased from Selleck.




製品説明 Dacomitinib (PF299804, PF299)は一種の有効で、不可逆的なパン(pan)ErbB阻害剤で、EGFRに作用する効果が一番強くて、無細胞試験でこのIC50値が6 nMです。Dacomitinib (PF299804, PF299)は EGFR或いはERBB2の突然変異型(耐Gefitinib)とEGFR T790M突然変異型を持っているNSCLCsに有効に作用します。臨床2期。
EGFR [1]
(Cell-free assay)
ErbB2 [1]
(Cell-free assay)
ErbB4 [1]
(Cell-free assay)
6.0 nM 45.7 nM 73.7 nM
In vitro試験

PF299804 is a specific inhibitor of the ERBB family of kinases. PF299804 inhibits EGFR signaling and induces apoptosis in the EGFR T790M-containing H3255 GR cell line. PF299804 is effective in gefitinib-sensitive and gefitinibresistant NSCLC cell lines. PF299804 inhibits the growth of H3255 and HCC827 cells engineered to express EGFR T790M. PF299804 inhibits EGFR phosphorylation in the presence of the T790M mutation. [1] PF-299804 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. [2] PF299804 shows significant growth-inhibitory effects in HER2-amplified gastric cancer cells (SNU216, N87), and it has lower 50% inhibitory concentration values compared with other EGFR tyrosine kinase inhibitors, including gefitinib, lapatinib, BIBW-2992, and CI-1033. PF299804 induces apoptosis and G1 arrest and inhibits phosphorylation of receptors in the HER family and downstream signaling pathways including STAT3, AKT, and extracellular signal-regulated kinases (ERK) in HER2-amplified gastric cancer cells. PF299804 also blocks EGFR/HER2, HER2/HER3, and HER3/HER4 heterodimer formation as well as the association of HER3 with p85α in SNU216 cells. [3] A recent research uses forty-seven human breast cancer and immortalized breast epithelial lines to evaluate the inhibition effects of PF299804, the results indicate PF299804 preferentially inhibits growth of HER-2-amplified breast cancer cell lines than nonamplified lines (RR = 3.39, p < 0.0001). PF299804 reduces the phosphorylation of HER2, EGFR, HER4, AKT, and ERK in the majority of sensitive lines. PF299804 exerts its anti-proliferative effect through a combined G0/G1 arrest and an induction of apoptosis. [4]

In vivo試験 Orally administered PF299804 effectively inhibits growth of HCC827 Del/T790M xenografts. [1] Low oral administration of PF-299804 (15mg/kg) causes significant antitumor activity, including marked tumor regressions in a variety of human tumor xenograft models that express and/ or overexpress ERBB family members or contain the double mutation (L858R/T790M) in ERBB1 (EGFR) associated with resistance to gefitinib and erlotinib. [2]


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ELISA-Based ERBB Kinase Assay:

The ERBB1, ERBB 2, and ERBB4 cytoplasmic fusion proteins are made by cloning the ERBB1 sequence (Met-668 to Ala-1211), ERBB2 (Ile-675 to Val-1256), and ERBB4 sequence (Gly-259 to Gly-690) into the baculoviral vector pFastBac using PCR. Proteins are expressed in baculovirusinfected Sf9 insect cells as GST fusion proteins. The proteins are purified by affinity chromatography using glutathione sepharose beads. Inhibition of ERBB tyrosine kinase activity is assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 μM ATP, PF299804 or vehicle control, and 1-5 nM GST-erbB per 50 μL of reaction mixture) are run in 96-well plates coated with 0.25 mg/mL poly-Glu-Tyr. The reactions are incubated for 6 minutes at room temperature while being shaken. Kinase reactions are stopped by removal of the reaction mixture, and then the wells are washed with wash buffer (0.1% Tween 20 in PBS). Phosphorylated tyrosine residues are detected by adding 0.2 μg/mL antiphosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to horseradish peroxidase (HRP) diluted in PBS containing 3% BSA and 0.05% Tween 20 for 25 minutes while being shaken at room temperature. The antibody is removed, and plates are washed in wash buffer. HRP substrate (SureBlue3,3,5,5-tetramethyl benzidine or TMB) is added (50 μL per well) and incubated for 10-20 minutes while it is shaken at room temperature. The TMB reaction is stopped with the addition of 50 μL of stop solution (0.09 N H2SO4). The signal is quantified by measuring absorbance at 450 nm. IC50 values are determined for PF299804 using the median effect method.
細胞アッセイ: [1]
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  • 細胞株: Various NSCLC cell lines
  • 濃度: 0-20 nM
  • 反応時間: 72 hours
  • 実験の流れ: 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.
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  • 動物モデル: HCC827-GFP or HCC827-Del/T790M lung cancer cells (in 0.2 mL of PBS) are inoculated s.c. into the lower-right quadrant of the flank of nude mice
  • 製剤: PF299804 is dissolved in DMSO in 10 mM at -20 °
  • 投薬量: 10 mg/kg
  • 投与方法: Administered via oral gavage

溶解度 (25°C)

体外 DMSO 19 mg/mL (40.43 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
体内 1% DMSO+30% polyethylene glycol+1% Tween 80, pH 9 10 mg/mL

* <1 mg/mlは製品が微弱に溶解する或いは溶解しないことを示します。
* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。


分子量 469.94


CAS No. 1110813-31-4
in solvent
別名 N/A





マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)


  • マス




貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積


この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1



  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):




チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2


マス 濃度 ボリューム 分子量


NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02382796 Recruiting NSCLC Pfizer July 2015 Phase 2
NCT02268747 Active, not recruiting Skin Squamous Cell Cancer Fondazione IRCCS Istituto Nazionale dei Tumori, Milano November 2014 Phase 2
NCT02097433 Completed Healthy Pfizer July 2014 Phase 1
NCT02047747 Terminated Brain Cancer David Piccioni, M.D., Ph.D|Pfizer|University of California, San Diego February 2014 Phase 2
NCT02039336 Recruiting Colorectal Cancer The Netherlands Cancer Institute|Pfizer January 2014 Phase 1|Phase 2
NCT01920061 Recruiting Neoplasm Pfizer September 2013 Phase 1



Handling Instructions


  • * 必須


EGFR Inhibitors with Unique Features


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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID