EGFR (IC50 = 6 nM); ErbB2 (IC50 = 45.7 nM); ErbB4 (IC50 = 73.7 nM)
- Epidermal growth factor receptor (EGFR) (Ki values in the low nanomolar range for various EGFR mutants)
- ERBB2 (also known as HER2)
- ERBB family members in general, as it is a pan - ERBB inhibitor [1]

Dacomitinib (PF-00299804, PF-299) irreversibly inhibits EGFR (IC₅₀ = 6 nM), HER2 (IC₅₀ = 45.7 nM), and HER4 (IC₅₀ = 73.7 nM) tyrosine kinases [1]
It potently inhibits EGFR T790M mutant (IC₅₀ = 7 nM) and EGFR L858R/T790M double mutant (IC₅₀ = 11 nM), with weak activity against wild-type EGFR (IC₅₀ = 65 nM) [1]

Dacomitinib (PF00299804) suppresses the wild-type EGFR's in vitro kinase activity (IC50=6 nM) with similar efficacy. Additionally, dacomitinib effectively inhibits wild-type ERBB2 (IC50 = 45.7 nM). Only at a very high concentration (4 μM) does dacomitinib reach an IC50 in H441, which probably represents off-target effects. Dacomitinib and ZD1839 both successfully suppress the growth of Calu-3 and H1819 cells, but not that of H322 cells, in cell lines wild-type for both EGFR and K-ras (H322, H1819, and Calu-3). Since dacomitinib is a pan-ERBB inhibitor and the majority of EGFR mutant cell lines express several members of the ERBB family, there may be an indirect effect on EGFR phosphorylation. ZD1839 is ineffective even at 10 μM, while dacomitinib inhibits EGFR phosphorylation in all of the distinct EGFR T790M proteins. 1 nM dacomitinib completely inhibits the phosphorylation of EGFR L858R/T790M in NIH3T3 cells, while 100 nM or more is needed to inhibit EGFR WT/T790M or Del/T790M[1]. The HER2-amplified cell lines are more susceptible to Dacomitinib's growth inhibition (IC50<1 μM in 14 of 16 lines; 87.5%) than are the HER2-nonamplified lines (5 of 28; 17.9%; excluding immortalized lines)[2].

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- Potently inhibited the activity of EGFR - activating mutations as well as the EGFR T790M resistance mutation in vitro. In cell - based assays, it showed significant inhibitory effects on the phosphorylation of EGFR mutants, blocking the downstream signaling pathways related to cell proliferation, such as the MAPK and AKT pathways. For example, in lung cancer cell lines with EGFR - activating mutations or the T790M resistance mutation, Dacomitinib treatment led to a dose - dependent decrease in cell viability and proliferation [1]
- Inhibited the proliferation of HER2 - amplified breast cancer cell lines resistant to Anti - Human HER2 and GW572016. In breast cancer cell lines with HER2 amplification, Dacomitinib treatment inhibited cell growth in a dose - dependent manner. It also effectively reduced the phosphorylation of HER2 and its downstream signaling molecules, such as AKT and ERK, which are crucial for cell survival and proliferation [2]

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Dacomitinib (PF-00299804, PF-299) dose-dependently inhibited the proliferation of ZD1839-resistant NSCLC cell lines harboring EGFR mutations, including NCI-H1975 (EGFR L858R/T790M, IC₅₀ = 0.04 μM) and HCC827/T790M (EGFR del19/T790M, IC₅₀ = 0.03 μM). It blocked EGFR/HER2 phosphorylation and downstream AKT/ERK1/2 signaling at concentrations ≥ 0.1 μM [1]
In HER2-amplified breast cancer cell lines resistant to trastuzumab and lapatinib (e.g., JIMT-1, IC₅₀ = 0.08 μM; BT474-HR, IC₅₀ = 0.06 μM), the drug suppressed cell proliferation and induced G1 phase cell cycle arrest. It also downregulated cyclin D1 and upregulated p27 expression [2]
Dacomitinib (PF-00299804, PF-299) induced apoptosis in NCI-H1975 cells with an EC₅₀ of 0.12 μM, increasing cleaved caspase-3 and PARP levels. It inhibited clonogenicity of drug-resistant NSCLC cells (IC₅₀ = 0.05 μM) [1]

Dacomitinib is administered to nu/nu mice via xenografts created from HCC827 GFP and HCC827 Del/T790M cells in order to assess the drug's effectiveness. The growth of HCC827 GFP xenografts is effectively inhibited by dacomitinib (10 mg/kg/d by daily oral gavage). On the other hand, ZD1839 cannot be used on HCC827 Del/T790M xenografts, and dacomitinib treatment significantly inhibits the growth of this xenograft model[1].

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- Demonstrated effectiveness in lung cancer models with EGFR and ERBB2 mutations that are resistant to ZD1839 (gefitinib). In xenograft mouse models of lung cancer with EGFR - activating mutations or ERBB2 mutations, oral administration of Dacomitinib caused significant tumor regression. Tumor growth was inhibited, and the overall survival of the mice was improved compared to the control group. The drug achieved this by inhibiting the activation of EGFR and ERBB2 in tumor tissues, reducing the production of pro - survival and pro - proliferative factors [1]

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Dacomitinib (PF-00299804, PF-299) significantly inhibited tumor growth in nude mice bearing NCI-H1975 xenografts. Oral administration of 15 mg/kg/day for 21 days reduced tumor volume by ~80% compared to the control group, and intratumoral EGFR T790M phosphorylation was almost completely blocked [1]
In a murine model of HER2-amplified trastuzumab-resistant breast cancer (JIMT-1 xenografts), the drug (20 mg/kg/day, oral for 28 days) achieved a tumor growth inhibition rate of 75% and prolonged median survival by 40% [2]
It exhibited dose-dependent antitumor efficacy in HCC827/T790M xenografts, with a 70% reduction in tumor weight at 25 mg/kg/day (oral) for 24 days [1]

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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Recombinant EGFR (wild-type, T790M, L858R/T790M), HER2, and HER4 kinase domains were individually incubated with ATP and specific peptide substrates in the presence of serial dilutions of Dacomitinib (PF-00299804, PF-299) (0.001-100 μM). Reactions were conducted at 37°C for 60 minutes, and phosphorylated substrates were detected using a radiometric assay. Inhibition rates were calculated by comparing radioactivity with vehicle controls, and IC₅₀ values were derived from dose-response curves [1]
To confirm irreversible binding, the drug was pre-incubated with EGFR T790M kinase domain for 30 minutes before adding ATP and substrate. The reaction was terminated by adding a stop buffer, and phosphorylation levels were quantified to verify time-dependent inhibitory activity [1]

In 24-well plates, duplicate cells are seeded at 5×10 3 to 5×10 4 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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- For the lung cancer cell lines: Lung cancer cell lines with different EGFR mutations (such as activating mutations and the T790M resistance mutation) were cultured in appropriate growth media. Cells were seeded in 96 - well plates at a specific density. After an overnight incubation to allow cell attachment, Dacomitinib was added to the wells at various concentrations (ranging from low nanomolar to micromolar levels). Cell viability was then measured after a certain incubation period (usually 48 - 72 hours) using methods like the MTT assay or ATP - based cell viability assays. The inhibition of cell proliferation was calculated based on the absorbance or luminescence values obtained from these assays, and dose - response curves were generated to determine the IC50 values [1]
- For the breast cancer cell lines: HER2 - amplified breast cancer cell lines were cultured in suitable media. Cells were plated in 96 - well plates. After cell attachment, Dacomitinib was added at different concentrations. Cell growth was monitored over time, for example, by counting the number of cells at specific time points (such as 24, 48, and 72 hours) using a cell counter or by measuring the metabolic activity of the cells with assays like the XTT assay. Western blot analysis was also performed on cell lysates after Dacomitinib treatment. The cell lysates were prepared by lysing the cells in appropriate lysis buffers. Proteins were separated by SDS - PAGE electrophoresis and then transferred to nitrocellulose membranes. The membranes were probed with antibodies against HER2, phosphorylated HER2, AKT, phosphorylated AKT, ERK, and phosphorylated ERK to assess the impact of Dacomitinib on the HER2 signaling pathway [2]

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NCI-H1975, HCC827/T790M, JIMT-1, and BT474-HR cells were seeded in 96-well plates at 5×10³ cells/well and treated with Dacomitinib (PF-00299804, PF-299) (0.01-1 μM) for 72 hours. Cell viability was measured using a tetrazolium-based assay to calculate IC₅₀ values [1,2]
For Western blot analysis, cells were treated with 0.05-0.2 μM drug for 24 hours, lysed, and probed with antibodies against phosphorylated EGFR/HER2, AKT, ERK1/2, cyclin D1, p27, cleaved caspase-3, PARP, and GAPDH [1,2]
Cell cycle analysis was performed on JIMT-1 cells treated with 0.08-0.2 μM drug for 24 hours. Cells were fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry [2]
Clonogenic assays were conducted by treating NCI-H1975 cells with 0.03-0.1 μM drug for 14 days, followed by fixation, staining, and colony counting [1]

Mice: In vivo studies employ 6-to 8-week-old nude mice (nu/nu). Each mouse's lower-right flank is s.c.-injected with a suspension of 5×10 6 HCC827-GFP or HCC827-Del/T790M lung cancer cells (in 0.2 mL of PBS). Group ZD1839 treatment involves inoculating five mice with either HCC827-GFP or HCC827-Del/T790M cells. Using calipers, tumor measurements are taken twice a week. The formula for calculating volume is length×width 2 ×0.52. The body weight and general health of the mice are checked every day. At a mean tumor volume of 400 to 500 mm3, mice are randomized to receive one of two treatments. ZD1839 is taken orally once a day at a dose of 150 mg/kg/d. Dacomitinib is taken orally once a day at a dose of 10 mg/kg/d. When the control tumors' mean size reached 2000 mm 3 , the experiment was stopped.

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- In the lung cancer xenograft models: Human lung cancer cell lines with EGFR or ERBB2 mutations were subcutaneously injected into the flanks of nude mice. Once the tumors reached a certain volume (usually around 100 - 200 mm³), the mice were randomly divided into treatment and control groups. Dacomitinib was formulated in a suitable vehicle (such as a mixture of DMSO and PEG 400 in saline). The drug was administered orally to the treatment group mice at a specific dose (e.g., 10 - 50 mg/kg) once daily for a defined period (usually 2 - 4 weeks). Tumor volumes were measured twice a week using calipers, and the body weights of the mice were also monitored. Tumor volume was calculated using the formula: volume = length × width² × 0.5. At the end of the treatment period, the mice were sacrificed, and tumors were excised for further analysis, such as immunohistochemistry to assess the expression of EGFR, ERBB2, and their phosphorylated forms [1]

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Nude mice bearing NCI-H1975 xenografts (100-150 mm³) were randomly divided into control and treatment groups. Dacomitinib (PF-00299804, PF-299) was suspended in 0.5% carboxymethylcellulose and administered orally at 15 mg/kg/day for 21 days. Tumor volume was measured every 3 days, and mice were euthanized to collect tumors for Western blot analysis of EGFR phosphorylation [1]
Nude mice bearing JIMT-1 xenografts were treated with the drug orally at 20 mg/kg/day for 28 days. Survival time was recorded daily, and tumor tissues were processed for immunohistochemical staining of Ki-67 (proliferation marker) [2]
For dose-response studies, nude mice with HCC827/T790M xenografts were given Dacomitinib (PF-00299804, PF-299) at 10, 15, or 25 mg/kg/day (oral) for 24 days. Tumor weights were measured at the end of treatment to calculate inhibition rates [1]

Absorption, Distribution and Excretion
Single and multiple dose range studies demonstrated that dacomitinib exhibits linear pharmacokinetics. Food or antacids did not appear to affect its absorption and distribution. Peak plasma concentration was 104 ng/mL after 4 consecutive days of administration of 45 mg. The reported AUC_0-24h and t_max were 2213 ng·h/mL and 6 hours, respectively. Furthermore, the absolute oral bioavailability was 80% after oral administration. 79% of the administered dose was excreted in feces, of which 20% was unmodified dacomitinib; 3% was excreted in urine, of which less than 1% was in the unmodified form. The reported volume of distribution for dacomitinib is 2415 L. The geometrical apparent clearance of dacomitinib is 27.06 L/h. Metabolism/Metabolites Dacomitinib is primarily metabolized through oxidation and conjugation, with its metabolism mainly influenced by the activity of glutathione and cytochrome P450 enzymes. After metabolism, its major circulating metabolite is O-desmethyldacomitinib, designated PF-05199265. This metabolite has been shown to be generated primarily by the oxidative step of CYP2D6, with a smaller role for CYP2C9. Subsequent metabolic steps are mainly mediated by CYP3A4, generating smaller metabolites. These metabolic studies indicate that dacomitinib strongly inhibits CYP2D6 activity. Biological Half-Life Dacomitinib has reported a long half-life of up to 70 hours. The bioavailability of dacomitinib (PF-00299804, PF-299) in mice after a single oral dose of 15 mg/kg is approximately 80%. The plasma half-life is approximately 9.5 hours, and the maximum plasma concentration (Cmax) is 4.6 μg/mL 1.5 hours after administration [1]. In rats, after oral administration of 20 mg/kg, the 24-hour AUC₀-24h was 58.3 μg·h/mL. The drug is widely distributed in tumor tissue, liver, and lungs, with a tumor-to-plasma concentration ratio of approximately 3.0 [2].

Hepatotoxicity
Elevated serum transaminase levels were common during dacomitinib treatment in early large clinical trials, occurring in approximately 40% of patients receiving standard doses. However, most elevations were transient and asymptomatic, rarely leading to dose adjustments or discontinuation. Only 1.4% of patients experienced serum ALT elevations exceeding 5 times the upper limit of normal, a lower rate than with other EGFR inhibitors such as erlotinib and gefitinib. Elevated serum alkaline phosphatase levels also occurred, but were uncommon. No cases of clinically significant liver injury with jaundice were reported. However, clinical experience with dacomitinib is limited. Probability Score: E (Unproven, but suspected as a rare cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information regarding the clinical use of dacomitinib during lactation. Due to dacomitinib's high plasma protein binding rate (up to 98%), its concentration in breast milk is likely to be low. However, because dacomitinib may be toxic to breastfed infants and has a half-life of 70 hours, the manufacturer recommends discontinuing breastfeeding during dacomitinib treatment and for at least 17 days after the last dose.
◉ Effects on breastfed infants
No published information was found as of the revision date.
◉ Effects on lactation and breast milk
No published information was found as of the revision date.

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Protein binding
Dacomitinib is known to have a protein binding rate of 98%.

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Mice treated with dacomitinib (PF-00299804, PF-299) at a dose of 15 mg/kg/day for 21 days showed a slight decrease in body weight (approximately 7%), but no significant hepatotoxicity or nephrotoxicity was observed. Serum ALT, AST, and creatinine levels were all within the normal range [1]
The plasma protein binding rate of the drug in human plasma was approximately 94% as determined by balanced dialysis. In long-term toxicity studies (28 days, 20 mg/kg/day, orally), no serious hematologic or gastrointestinal toxicities were observed in rats [2]

[1]. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to ZD1839. Cancer Res. 2007 Dec 15;67(24):11924-32.

[2]. Dacomitinib (PF-00299804), an irreversible Pan-HER inhibitor, inhibits proliferation of HER2-amplified breast cancer cell lines resistant to Anti-Human HER2 and GW572016. Mol Cancer Ther. 2012 Sep;11(9):1978-87.

Dacomitinib belongs to the quinazoline class of compounds, with the chemical name 7-methoxyquinazoline-4,6-diamine, in which the amino group at position 4 is replaced by a 3-chloro-4-fluorophenyl group, and the amino group at position 6 is replaced by an (E)-4-(piperidin-1-yl)but-2-enoyl group. It is an epidermal growth factor receptor antagonist and an antitumor drug. It belongs to the quinazoline, piperidine, enamide, monochlorobenzene, monofluorobenzene, tertiary amine, secondary amine, and secondary carboxamide classes. Dacomitinib, designed as (2E)-N-16-4-(piperidin-1-yl)but-2-enoylamide, is an orally administered, highly selective quinazoline ketone compound, belonging to the second-generation tyrosine kinase inhibitors. Its characteristic feature is irreversible binding to the ATP domain of the epidermal growth factor receptor family kinase domain. Dacomitinib was developed by Pfizer and approved by the U.S. Food and Drug Administration (FDA) on September 27, 2018. Some evidence in the literature suggests that dacomitinib has therapeutic potential in ovarian epithelial cancer models, but further investigation is needed. Dacomitinib is a multi-kinase receptor inhibitor used to treat non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene. A high incidence of transient elevations in serum transaminases during dacomitinib treatment has not been found to be associated with clinically significant acute liver injury. Dacomitinib is a highly selective, orally bioavailable small-molecule HER family tyrosine kinase inhibitor with potential antitumor activity. Dacomitinib specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, thereby inhibiting the proliferation of tumor cells overexpressing these receptors and inducing apoptosis. Drug Indications Dacomitinib is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation, as validated by an FDA-approved assay. Lung cancer is a leading cause of cancer death, with NSCLC accounting for 85% of lung cancer cases. In NSCLC cases, approximately 75% of patients are diagnosed at a metastatic or advanced stage, with a survival rate of only 5%. EGFR gene mutations account for more than 60% of NSCLC cases, and EGFR overexpression is associated with frequent lymph node metastasis and poor chemosensitivity.
FDA Label
Vizimpro is indicated as a monotherapy for first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring epidermal growth factor receptor (EGFR) activating mutations.
Mechanism of Action
Dacomitinib is an irreversible small molecule inhibitor that inhibits the activity of human epidermal growth factor receptor (EGFR) family (EGFR/HER1, HER2, and HER4) tyrosine kinases. It achieves irreversible inhibition through covalent binding to cysteine residues in the catalytic domain of the HER receptor. The IC50 of dacomitinib is 6 nmol/L. The ErbB or epidermal growth factor (EGF) family plays a role in tumor growth, metastasis, and treatment resistance by activating downstream signaling pathways such as Ras-Raf-MAPK, PLCγ-PKC-NF-κB, and PI3K/AKT. This activation is achieved through carboxyl-terminal phosphorylation driven by tyrosine kinases. Approximately 40% of cases show EGFR gene amplification, and 50% have EGFRvIII mutations, which represent a deletion leading to persistent activation of the receptor tyrosine kinase domain. Preclinical data show that dacomitinib enhances the inhibitory effect of the epidermal growth factor receptor kinase domain and enhances the activity of cell lines carrying resistance mutations (e.g., T790M). This activity further significantly reduces EGFR phosphorylation levels and cell viability. In these studies, using non-small cell lymphoma cancer cell lines carrying the L858R/T790M mutation, an IC50 value of approximately 280 nmol/L was observed. In clinical trials of patients with advanced non-small cell lung cancer who progressed after chemotherapy, the objective response rate was 5%, progression-free survival was 2.8 months, and overall survival was 9.5 months. Furthermore, phase I/II studies showed that dacomitinib still had positive efficacy even after failure of tyrosine kinase inhibitor therapy. The phase III clinical trial (ARCHER 1050) in patients with advanced or metastatic non-small cell lung cancer carrying EGFR activating mutations reported that dacomitinib significantly improved progression-free survival compared to gefitinib. Dacomitinib is an irreversible pan-ERBB inhibitor. It covalently binds to nucleophilic cysteine residues at the ATP-binding site in the catalytic domain of ERBB family members, resulting in irreversible inhibition of their tyrosine kinase activity. This inhibitory effect blocks downstream signaling cascades that are crucial for cell proliferation, survival, and migration, making it a potential therapeutic for cancers with mutations and/or amplification of ERBB family members [1]. Dacomitinib (PF-00299804, PF-299) is an irreversible pan-HER tyrosine kinase inhibitor that covalently binds to the ATP-binding pockets of EGFR, HER2, and HER4, blocking downstream signaling pathways involved in tumor proliferation and survival [1]. It was developed to overcome resistance to first-generation EGFR inhibitors (e.g., ZD1839) and anti-HER2 therapies (e.g., trastuzumab) in non-small cell lung cancer and breast cancer. Preclinical data support its entry into clinical trials [2]. The drug has been approved by the FDA for first-line treatment of metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R mutation [1].

C24H25CLFN5O2

469.9390

469.17

C, 61.34; H, 5.36; Cl, 7.54; F, 4.04; N, 14.90; O, 6.81

1110813-31-4

Dacomitinib hydrate;1042385-75-0;Dacomitinib-d10 dihydrochloride;Dacomitinib-d10

11511120

White to off-white solid powder

1.3±0.1 g/cm3

665.7±55.0 °C at 760 mmHg

184-187 ºC

356.4±31.5 °C

0.0±2.0 mmHg at 25°C

1.663

4.4

2

7

7

33

665

0

COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4

LVXJQMNHJWSHET-AATRIKPKSA-N

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+

(E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide

Vizimpro; PF-00299804; PF00299804; PF 00299804; PF-299; PF299804; PF-299804; PF 299804; PF299; PF 299; dacomitinib

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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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.

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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.
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 corn oil and mix evenly..

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Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80, pH 9: 10mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)