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| 25mg |
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| 100mg |
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Purity: ≥98%
Dacomitinib (formerly aslo known as PF299804, PF299; trade name: Vizimpro) is an orally bioavailable, highly selective, irreversible/covalent, 2nd generation pan-ErbB inhibitor, mostly to EGFR, with IC50 values of 6 nM, 45.7 nM and 73.7 nM for inhibiting EGFR, ERBB2, and ERBB4, respectively in cell-free assays. It is effective against NSCLCs with the EGFR T790M mutation and those with EGFR or ERBB2 mutations that are resistant to gefitinib. It may also have potential antineoplastic activity. The FDA approved dacomitinib as a first-line medication for the treatment of non-small cell lung cancer on September 29, 2018.
| Targets |
EGFR (IC50 = 6 nM); ErbB2 (IC50 = 45.7 nM); ErbB4 (IC50 = 73.7 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The ERBB1 sequence (Met-668 to Ala-1211), ERBB2 sequence (Ile-675 to Val-1256), and ERBB4 sequence (Gly-259 to Gly-690) are cloned using PCR into the baculoviral vector pFastBac to create the ERBB1, ERBB2, and ERBB4 cytoplasmic fusion proteins. In Sf9 insect cells infected with baculovirus, proteins are expressed as GST fusion proteins. Glutathione sepharose beads are used in affinity chromatography to purify the proteins. An ELISA-based receptor tyrosine kinase assay is used to measure inhibition of ERBB tyrosine kinase activity. In 96-well plates coated with 0.25 mg/mL poly-Glu-Tyr, kinase reactions are conducted with the following conditions: 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. The reactions are shaken and allowed to incubate for six minutes at room temperature. After removing the reaction mixture to halt the kinase reactions, the wells are cleaned using wash buffer (0.1% Tween 20 in PBS). The detection of phosphorylated tyrosine residues involves the addition of 0.2 μg/mL antiphosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) in combination with diluted horseradish peroxidase (HRP) in PBS containing 3% BSA and 0.05% Tween 20. The mixture is then shaken at room temperature for 25 minutes. After the antibody is eliminated, wash buffer is used to wash the plates. 50 μL of the HRP substrate (SureBlue3,3,5,5-tetramethyl benzidine, or TMB) is added to each well, and it is shaken at room temperature for 10 to 20 minutes of incubation. 50 μL of the stop solution (0.09 N H2SO4) is added to the TMB reaction to halt it. The absorbance at 450 nm is used to quantify the signal. The median effect method is utilized to ascertain the IC50 values for PF299804.
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| Cell Assay |
In 24-well plates, duplicate cells are seeded at 5×103 to 5×104 cells per well, and growth inhibition data is computed. In short, a dose-response curve is generated by adding Dacomitinib at 10 μM and performing 2-fold dilutions over a range of 12 concentrations the day after plating. Also seeded are control wells devoid of the medication. The cells are counted when the drug is added on day 1 and again when the experiment is over, which is six days later. Using a Coulter Z1 particle counter, cells are counted as soon as they are placed in an isotone solution following trypsinization. Using a Coulter Vi-Cell counter, the suspension cultures are tallied[2].
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| References |
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| Molecular Formula |
C24H25CLFN5O2
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| Molecular Weight |
469.94
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| Exact Mass |
469.17
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| Elemental Analysis |
C, 61.34; H, 5.36; Cl, 7.54; F, 4.04; N, 14.90; O, 6.81
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| CAS # |
1110813-31-4
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| Related CAS # |
Dacomitinib hydrate;1042385-75-0;Dacomitinib-d10 dihydrochloride;Dacomitinib-d10
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| Appearance |
White to off-white solid powder
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| SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4
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| InChi Key |
LVXJQMNHJWSHET-AATRIKPKSA-N
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| InChi Code |
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+
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| Chemical Name |
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
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| Synonyms |
Vizimpro; PF-00299804; PF00299804; PF 00299804; PF-299; PF299804; PF-299804; PF 299804; PF299; PF 299; dacomitinib
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.32 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80, pH 9: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1279 mL | 10.6397 mL | 21.2793 mL | |
| 5 mM | 0.4256 mL | 2.1279 mL | 4.2559 mL | |
| 10 mM | 0.2128 mL | 1.0640 mL | 2.1279 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04768491 | Recruiting | Drug: Dacomitinib | NSCLC Stage IV EGFR Activating Mutation |
Peking Union Medical College | September 1, 2020 | |
| NCT04946968 | Recruiting | Drug: Oral Dacomitinib | Advanced Solid Tumours Non-small Cell Lung Cancer |
National Cancer Centre, Singapore | August 24, 2021 | Phase 2 |
| NCT04027647 | Active Recruiting |
Drug: Dacomitinib | NSCLC Stage IIIB NSCLC Stage IIIC |
National Cancer Centre, Singapore | September 11, 2019 | Phase 2 |
| NCT04155541 | Recruiting | Drug: dacomitinib hydrate | EGFR Mutation-positive Inoperable or Reccrent NSCLC |
Pfizer | January 24, 2020 | |
| NCT03810807 | Active Recruiting |
Drug: Dacomitinib Drug: Osimertinib |
Metastatic Non-small Cell Lung Cancer |
Memorial Sloan Kettering Cancer Center |
January 17, 2019 | Phase 1 |
Inhibitory concentration and cell type.
Effects of dacomitinib on cell cycle.Cancer Res.2007 Dec 15;67(24):11924-32. |
The effects of dacomitinib on total and phosphorylated HER2, EGFR, HER4, AKT, and ERK.
Chemical structures of investigated molecules in this article.Cancer Res.2007 Dec 15;67(24):11924-32. |
Effects of dacomitinib on apoptosis.Cancer Res.2007 Dec 15;67(24):11924-32. |
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