Cited by 1,009Computational Drug Discovery MethodsProtein Kinase Regulation and GTPase SignalingCancer Mechanisms and Therapy

Kinase inhibitors: the road ahead

Ferguson, Fleur M., Gray, Nathanael S.·2018·Nature Reviews Drug Discovery

Abstract

Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been firmly demonstrated to play an essential role in virtually all major disease areas. Kinase inhibitor drug discovery programmes have recently broadened their focus to include an expanded range of kinase targets and therapeutic areas. In this Review, we provide an overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors.

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Crossref · 10.1038/nrd.2018.21

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  • The highly conserved ATP-binding site of the more than 500 kinases encoded in the human genome makes discovery of selective inhibitors challenging and often unachievable.

    “The highly conserved ATP-binding site of the more than 500 kinases encoded in the human genome makes the discovery of selective inhibitors a challenging and an often unachievable venture.6,7”

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Authors
Ferguson, F. M., & Gray, N. S.
Affiliations
Harvard University (US)
Corresponding author
Gray, Nathanael S.
Venue
Nature Reviews Drug Discovery
Published
2018-03-16
Volume
17
Issue
5
Pages
353-377
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W2794211762
Cited by
1,009
References
292
Citations by year
2026: 75 · 2025: 87 · 2024: 120 · 2023: 95 · 2022: 119 · 2021: 204 · 2020: 152 · 2019: 113 · 2018: 44
FWCI
10.29
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
Keywords
kinase inhibitors, receptor tyrosine kinase, cancer therapy, angiogenesis inhibition, degenerative diseases, inflammatory diseases, infectious diseases, selectivity profiling, computer-aided drug design, medicinal chemistry, small molecule drug discovery
MeSH terms
Animals, Antineoplastic Agents, Humans, Neovascularization, Pathologic, Signal Transduction, Protein Kinase Inhibitors, Small Molecule Libraries, Drug Discovery

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