Abstract
Deregulation of kinase activity has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. To date, 11 kinase inhibitors have received US Food and Drug Administration approval as cancer treatments, and there are considerable efforts to develop selective small molecule inhibitors for a host of other kinases that are implicated in cancer and other diseases. Herein we discuss the current challenges in the field, such as designing selective inhibitors and developing strategies to overcome resistance mutations. This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors.
MeSH terms
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Allosteric Regulation / drug effects
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Binding Sites
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Drug Delivery Systems
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Drug Design
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Drug Discovery
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Drug Resistance, Neoplasm
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Humans
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Models, Molecular
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Neoplasms / drug therapy*
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Neoplasms / enzymology
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Protein Binding
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Protein Conformation
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Protein Kinase Inhibitors / classification
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Protein Kinases / chemistry
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Protein Kinases / genetics
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Protein Kinases / physiology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Substrate Specificity
Substances
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Antineoplastic Agents
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Neoplasm Proteins
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Protein Kinase Inhibitors
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Protein Kinases