Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor
Open accessPublished version of a preprint
Abstract
Signaling through the erbB receptor family of tyrosine kinases contributes to the proliferation, differentiation, migration, and survival of a variety of cell types. Abnormalities in members of this receptor family have been shown to play a role in oncogenesis, thus making them attractive targets for anticancer treatments. PF-00299804 is a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor currently in phase I clinical trials. PF-00299804 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. Oral administration of PF-00299804 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. Furthermore, PF-00299804 shows exceptional distribution to human tumor xenografts and excellent pharmacokinetic properties across species. [Mol Cancer Ther 2008;7(7):1880–9]
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References 51 · Cited by 226
Research works printed but not linked: 2
- Moy B, Kirkpatrick P, Kar S, Goss P. Lapatinib. Nat Rev Drug Discov 2007;6:431 -2.
- Corbett TH, Griswold DP, Jr., Roberts BJ, Peckham JC, Schabel FM, Jr. Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 1977;40:2660 -80.
- Authors
- Gonzales, A. J., Hook, K. E., Althaus, I. W., Ellis, P. A., Trachet, E., Delaney, A. M., Harvey, P. J., Ellis, T. A., Amato, D. M., Nelson, J. M., Fry, D. W., Zhu, T., Loi, C.-M., Fakhoury, S. A., Schlosser, K. M., Sexton, K. E., Winters, R. T., Reed, J. E., Bridges, A. J., Lettiere, D. J., Baker, D. A., Yang, J., Lee, H. T., Tecle, H., & Vincent, P. W.
- Affiliations
- 1Cancer Biology,
- 2Pharmacokinetics & Drug Metabolism, and
- Pfizer (United States) (US)
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2008-07-01
- Volume
- 7
- Issue
- 7
- Pages
- 1880-1889
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- OpenAlex
- W2112098753
- Cited by
- 226
- References
- 51
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 13 · 2022: 7 · 2021: 6 · 2020: 14 · 2019: 18 · 2018: 11 · 2017: 13 · 2016: 19 · 2015: 18 · 2014: 20 · 2013: 13 · 2012: 20
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- irreversible tyrosine kinase inhibitor, EGFR, gefitinib resistance, erlotinib resistance, anticancer activity, pharmacokinetics, tumor xenografts
- MeSH terms
- Animals, Antineoplastic Agents, Female, Humans, Mutation, Phosphorylation, Species Specificity, Mice, SCID, Amino Acid Substitution, Receptor Protein-Tyrosine Kinases, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice, Quinazolinones, ErbB Receptors
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