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Targeting the cancer kinome through polypharmacology
Open accessAbstract
Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.
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“We found no correlation between these variables, consistent with evidence that kinase inhibitor pharmacophores display a high degree of polypharmacology”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Knight et al., 2010
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Metadata
- Authors
- Knight, Z. A., Lin, H., & Shokat, K. M.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Knight, Zachary A.
- Shokat, Kevan M.
- Venue
- Nature reviews. Cancer
- Published
- 2010-02
- Volume
- 10
- Issue
- 2
- Pages
- 130-137
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC2880454
- OpenAlex
- W2022609682
- Cited by
- 674
- References
- 104
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 21 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 47 · 2019: 34 · 2018: 45 · 2017: 51 · 2016: 43 · 2015: 48 · 2014: 72 · 2013: 70 · 2012: 43
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r01eb001987-15)
- National Institute of Diabetes and Digestive and Kidney Diseases (R00DK083531, K99DK083531)
- National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Keywords
- kinase inhibitors, polypharmacology, combination therapy, drug resistance, anticancer drug development
- MeSH terms
- Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Mutation, Neoplasms, Protein Kinases, Technology, Pharmaceutical, Drug Delivery Systems, Drug Resistance, Neoplasm, RNA, Small Interfering, Protein Kinase Inhibitors, Drug Discovery
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