WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205576
CAS#: 1110813-31-4 (free)
Description: Dacomitinib, also known as PF-299 and PF-00299804 ; or PF299804, is an orally bioavailable, highly selective, second-generation small-molecule inhibitor of the pan-epidermal growth factor receptor (EGFR) family of tyrosine kinases (ErbB family) with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human EGFR subtypes, resulting in inhibition of proliferation and induction of apoptosis in EGFR-expressing tumor cells. EGFRs play major roles in tumor cell proliferation and tumor vascularization, and are often overexpressed or mutated in various tumor cell types.
Hodoodo Cat#: H205576
Name: Dacomitinib
CAS#: 1110813-31-4 (free)
Chemical Formula: C24H25ClFN5O2
Exact Mass: 469.17
Molecular Weight: 469.940
Elemental Analysis: C, 61.34; H, 5.36; Cl, 7.54; F, 4.04; N, 14.90; O, 6.81
Related CAS #: 1110813-31-4 (free) 1042385-75-0 (hydrate) 1262034-38-7
Synonym: PF-00299804; PF00299804; PF 00299804; PF299804; PF-299804; PF 299804; PF-299; PF299; PF 299; Dacomitinib; Vizimpro;
IUPAC/Chemical Name: (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide
InChi Key: LVXJQMNHJWSHET-AATRIKPKSA-N
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+
SMILES Code: O=C(NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OC)/C=C/CN4CCCCC4
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | 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. |
| In vitro activity: | Treatment with dacomitinib significantly reduced EGFRvIII phosphorylation (Y1173) at doses ranging from 0.4-4 μM. Inhibition of EGFRvIII phosphorylation was also observed by immunofluorescence in U87vIII.Luc2 cells exposed to dacomitinib in vitro (Figure 1B). Phosphorylation of downstream EGFR effectors AKT (S473) and ERK1/2 (T202/Y204) was also assessed in the U87.Luc2 and U87vIII.Luc2 cells (Figure 1A). Dacomitinib treatment decreased phosphorylation of both kinases, relative to EGF-stimulated/DMSO-treated controls, indicating that both receptor activity and downstream signaling was inhibited in glioblastoma cells. Similarly, in a short-term culture of GBM6 patient-derived glioblastoma cells that also harbor EGFR amplification and vIII-mediated activation, dacomitinib effectively blocked EGFR phosphorylation, and downstream AKT and ERK1/2 activation (Figure 1C). Reference: Neoplasia. 2018 May; 20(5): 432–442. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916087/ |
| In vivo activity: | The ADC value in necrotic tumor core of rats treated with Dacomitinib was lower than that of UT (untreatment) group. The inhibitory effect of Dacomitinib on necrotic tumor core of C6 glioma was observed on T2WI images in each group. The percentage of necrotic tumor volume in rats treated with Dacomitinib was lower compared with UT group, probably due to the fact that Dacomitinib affected necrosis by down-regulating genes related to Ca2+ channel signaling, thus reducing intracellular Ca2+. Microarray results also confirmed that Dacomitinib affected genes associated with Ca2+ channel signaling. Dacomitinib down-regulated the expression of MGP and MFAP-4, which were directly related to Ca2+ channel signaling. In addition, the expression of other genes related to Ca2+ channel signaling also seemed to be down-regulated by Dacomitinib. Since TNF-α is associated with Ca2+ channel related genes, the down-regulation of Ca2+-related genes may also down-regulate TNF-α expression, which in turn down-regulate NF-κB signaling pathway, thereby reducing cell necrosis. The expression of ADAMTS8 directly related to TNF-α was also down-regulated. Reference: Biosci Rep. 2019 Mar 29; 39(3): BSR20190006. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400661/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 45.3 | 96.46 | |
| Ethanol | 15.0 | 31.92 |
The following data is based on the product molecular weight 469.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Endersby R, Whitehouse J, Hii H, Greenall SA, Johns TG, Gottardo NG. A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors. Neoplasia. 2018 May;20(5):432-442. doi: 10.1016/j.neo.2018.02.004. Epub 2018 Mar 22. PMID: 29574250; PMCID: PMC5916087. 2. Momeny M, Zarrinrad G, Moghaddaskho F, Poursheikhani A, Sankanian G, Zaghal A, Mirshahvaladi S, Esmaeili F, Eyvani H, Barghi F, Sabourinejad Z, Alishahi Z, Yousefi H, Ghasemi R, Dardaei L, Bashash D, Chahardouli B, Dehpour AR, Tavakkoly-Bazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH. Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells. Sci Rep. 2017 Jun 23;7(1):4204. doi: 10.1038/s41598-017-04147-0. PMID: 28646172; PMCID: PMC5482808. 3. Chen WS, Hong L, Wang F, Li JJ. Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI. Biosci Rep. 2019 Mar 6;39(3):BSR20190006. doi: 10.1042/BSR20190006. PMID: 30782784; PMCID: PMC6400661. 4. Guo X, To KKW, Chen Z, Wang X, Zhang J, Luo M, Wang F, Yan S, Fu L. Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo. J Exp Clin Cancer Res. 2018 Feb 20;37(1):31. doi: 10.1186/s13046-018-0690-x. PMID: 29458405; PMCID: PMC5819299. |
| In vitro protocol: | 1. Endersby R, Whitehouse J, Hii H, Greenall SA, Johns TG, Gottardo NG. A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors. Neoplasia. 2018 May;20(5):432-442. doi: 10.1016/j.neo.2018.02.004. Epub 2018 Mar 22. PMID: 29574250; PMCID: PMC5916087. 2. Momeny M, Zarrinrad G, Moghaddaskho F, Poursheikhani A, Sankanian G, Zaghal A, Mirshahvaladi S, Esmaeili F, Eyvani H, Barghi F, Sabourinejad Z, Alishahi Z, Yousefi H, Ghasemi R, Dardaei L, Bashash D, Chahardouli B, Dehpour AR, Tavakkoly-Bazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH. Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells. Sci Rep. 2017 Jun 23;7(1):4204. doi: 10.1038/s41598-017-04147-0. PMID: 28646172; PMCID: PMC5482808. |
| In vivo protocol: | 1. Chen WS, Hong L, Wang F, Li JJ. Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI. Biosci Rep. 2019 Mar 6;39(3):BSR20190006. doi: 10.1042/BSR20190006. PMID: 30782784; PMCID: PMC6400661. 2. Guo X, To KKW, Chen Z, Wang X, Zhang J, Luo M, Wang F, Yan S, Fu L. Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo. J Exp Clin Cancer Res. 2018 Feb 20;37(1):31. doi: 10.1186/s13046-018-0690-x. PMID: 29458405; PMCID: PMC5819299. |
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