Dacomitinib (Synonyms: PF-00299804; PF-299804)

Name: Dacomitinib
Brand: MedChemExpress
SKU: HY-13272
Rating: 5.0 (21 reviews)

Cat. No.: HY-13272 Purity: 99.69%: FAQs
Data Sheet SDS COA Handling Instructions

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Dacomitinib (PF-00299804) is a specific and irreversible inhibitor of the ERBB family of kinases with IC₅₀s of 6 nM, 45.7 nM and 73.7 nM for EGFR, ERBB2, and ERBB4, respectively.

For research use only. We do not sell to patients.

Dacomitinib Chemical Structure

CAS No. : 1110813-31-4

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 101	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 101	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 92	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 158	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 290	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 450	In-stock	Estimated Time of Arrival: December 31
200 mg	USD 594	In-stock	Estimated Time of Arrival: December 31
500 mg		Get quote
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Based on 21 publication(s) in Google Scholar

Other Forms of Dacomitinib:

Dacomitinib-d5 Get quote
Dacomitinib-d₁₀ dihydrochloride Get quote
Dacomitinib-d₁₀ Get quote
Dacomitinib hydrate Get quote
Dacomitinib (Standard) Get quote

21 Publications Citing Use of MCE Dacomitinib

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EGFR/ErbB1/HER1 ErbB2/HER2 ErbB3/HER3 ErbB4/HER4

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

EGFR

6 nM (IC₅₀)

ErbB2

45.7 nM (IC₅₀)

ErbB4

73.7 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
LoVo	IC₅₀	0.011 μM Compound: 5	Inhibition of wild type EGFR phosphorylation in human LoVo cells after 2 hrs by fluorescence assay Inhibition of wild type EGFR phosphorylation in human LoVo cells after 2 hrs by fluorescence assay	[PMID: 23930994]
NCI-H1975	IC₅₀	0.042 μM Compound: 5	Inhibition of EGFR L858R/T970M double mutant phosphorylation in human NCI-H1975 cells after 2 hrs by fluorescence assay Inhibition of EGFR L858R/T970M double mutant phosphorylation in human NCI-H1975 cells after 2 hrs by fluorescence assay	[PMID: 23930994]
NCI-H1975	IC₅₀	0.44 μM Compound: 32; PF00299804	Antiproliferative activity against human NCI-H1975 cells expressing EGFR T790M/L858R mutant incubated for 72 hrs by MTS assay Antiproliferative activity against human NCI-H1975 cells expressing EGFR T790M/L858R mutant incubated for 72 hrs by MTS assay	[PMID: 28754471]
PC-9	IC₅₀	0.00063 μM Compound: 5	Inhibition of EGFR exon 19 deletion activating mutant phosphorylation in human PC9 cells after 2 hrs by fluorescence assay Inhibition of EGFR exon 19 deletion activating mutant phosphorylation in human PC9 cells after 2 hrs by fluorescence assay	[PMID: 23930994]
Sf9	IC₅₀	0.006 μM Compound: 54; PF-00299804	Irreversible inhibition of GST-tagged ERBB1 (unknown origin) (Met-668 to Ala-1211 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA Irreversible inhibition of GST-tagged ERBB1 (unknown origin) (Met-668 to Ala-1211 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA	[PMID: 27491023]
Sf9	IC₅₀	0.046 μM Compound: 54; PF-00299804	Irreversible inhibition of GST-tagged ERBB2 (unknown origin) (Ile-675 to Val-1256 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA Irreversible inhibition of GST-tagged ERBB2 (unknown origin) (Ile-675 to Val-1256 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA	[PMID: 27491023]
Sf9	IC₅₀	0.074 μM Compound: 54; PF-00299804	Irreversible inhibition of GST-tagged ERBB4 (unknown origin) (Gly-259 to Gly-690 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA Irreversible inhibition of GST-tagged ERBB4 (unknown origin) (Gly-259 to Gly-690 residues) expressed in baculovirus infected Sf9 insect cells assessed as reduction in Glu/Tyr copolymer phosphorylation after 6 mins by ELISA	[PMID: 27491023]
Sf9	IC₅₀	3.57 μM Compound: 54; PF-00299804	Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA	[PMID: 27491023]

In Vitro

Dacomitinib (PF00299804) effectively inhibits the in vitro kinase activity of wild-type EGFR (IC50=6 nM)with similar efficacy. Dacomitinib also effectively inhibits wild-type ERBB2 with IC₅₀ of 45.7 nM. In H441, an IC₅₀ is reached with Dacomitinib but only at a very high concentration (4 μM) and likely reflects off-target effects. In cell lines wild-type for both EGFR and K-ras (H322, H1819, and Calu-3), ZD1839 and Dacomitinib both effectively inhibit growth of H1819 and Calu-3 cells but not of H322 cells. Dacomitinib is a pan-ERBB inhibitor and most EGFR mutant cell lines express multiple ERBB family members, the effects on EGFR phosphorylation could potentially be indirect. Dacomitinib inhibits EGFR phosphorylation in all of the different EGFR T790M proteins whereas ZD1839 is ineffective even at 10 μM. In the NIH3T3 cells, phosphorylation of EGFR L858R/T790M is completely inhibited by 1 nM Dacomitinib, whereas 100 nM or greater is required to inhibit EGFR WT/T790M or Del/T790M^[1]. The HER2-amplified cell lines are most sensitive to growth inhibition by Dacomitinib (IC₅₀<1 μM in 14 of 16 lines; 87.5%) as compared with 5 of 28 (17.9%) of HER2-nonamplified lines (excluding immortalized lines)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

To evaluate the efficacy of Dacomitinib, xenografts in nu/nu mice are generated using HCC827 GFP and HCC827 Del/T790M cells and treated the mice with Dacomitinib. Dacomitinib (10 mg/kg/d by daily oral gavage) effectively inhibits the growth of HCC827 GFP xenografts. In contrast, HCC827 Del/T790M xenografts are resistant to ZD1839, whereas Dacomitinib treatment is substantially more effective at inhibiting growth of this xenograft model^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

469.94

Formula

C₂₄H₂₅ClFN₅O₂

CAS No.

1110813-31-4

Appearance

Solid

Color

White to yellow

SMILES

O=C(/C=C/CN1CCCCC1)NC2=CC3=C(C=C2OC)N=CN=C3NC4=CC=C(C(Cl)=C4)F

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 40 mg/mL (85.12 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.32 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.32 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 0.5% CMC/saline water
Solubility: 5 mg/mL (10.64 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.74%

Select Batch:

Data Sheet (282 KB) SDS (252 KB)

COA (252 KB) HNMR (214 KB) LCMS (350 KB) Elemental Analysis Report (110 KB)

Handling Instructions (2659 KB)

References

[1]. Engelman JA, et al. 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. [Content Brief]

[2]. Kalous O, et al. 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. [Content Brief]

Cell Assay ^[2]	Cells are seeded in duplicate at 5×10³ to 5×10⁴ cells per well in 24-well plates, and growth inhibition data is calculated. Briefly, day after plating, Dacomitinib is added at 10 μM and 2-fold dilutions over 12 concentrations are carried out to generate a dose-response curve. Control wells without the drug are also seeded. The cells are counted on day 1 when the drug is added, as well as after 6 days when the experiment ended. After the trypsinization cells are placed in an Isotone solution and immediately counted using a Coulter Z1 particle counter. The suspension cultures are counted using a Coulter Vi-Cell counter^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] Nude mice (nu/nu; 6-8 weeks old) are used for in vivo studies. A suspension of 5×10⁶ 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 each mouse. Five mice are inoculated with either HCC827-GFP or HCC827-Del/T790M cells in the ZD1839 treatment group. Tumors are measured twice weekly using calipers, and volume is calculated using the following formula: length×width²×0.52. Mice are monitored daily for body weight and general condition. Mice are randomized to treatment when the mean tumor volume is 400 to 500 mm³. ZD1839 is administered at 150 mg/kg/d by daily oral gavage. Dacomitinib is administered at 10 mg/kg/d by daily oral gavage. The experiment is terminated when the mean size of the control tumors reached 2000 mm³. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Engelman JA, et al. 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. [Content Brief] [2]. Kalous O, et al. 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. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.1279 mL	10.6397 mL	21.2793 mL	53.1983 mL
	5 mM	0.4256 mL	2.1279 mL	4.2559 mL	10.6397 mL
	10 mM	0.2128 mL	1.0640 mL	2.1279 mL	5.3198 mL
	15 mM	0.1419 mL	0.7093 mL	1.4186 mL	3.5466 mL
	20 mM	0.1064 mL	0.5320 mL	1.0640 mL	2.6599 mL
	25 mM	0.0851 mL	0.4256 mL	0.8512 mL	2.1279 mL
	30 mM	0.0709 mL	0.3547 mL	0.7093 mL	1.7733 mL
	40 mM	0.0532 mL	0.2660 mL	0.5320 mL	1.3300 mL
	50 mM	0.0426 mL	0.2128 mL	0.4256 mL	1.0640 mL
	60 mM	0.0355 mL	0.1773 mL	0.3547 mL	0.8866 mL
	80 mM	0.0266 mL	0.1330 mL	0.2660 mL	0.6650 mL

Dacomitinib Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Dacomitinib1110813-31-4PF-00299804 PF-299804PF00299804PF 00299804PF299804PF 299804PF-299804EGFRApoptosisEpidermal growth factor receptorErbB-1HER1Inhibitorinhibitorinhibit

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Dacomitinib (Synonyms: PF-00299804; PF-299804)

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Other Forms of Dacomitinib:

Dacomitinib Related Antibodies

21 Publications Citing Use of MCE Dacomitinib

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Biological Activity

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Purity & Documentation

References

Customer Review

Dacomitinib Related Antibodies

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Complete Stock Solution Preparation Table

Dacomitinib Related Classifications

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