Kinase inhibitors: the road ahead
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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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”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [7]
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Thermodynamic Contributions of the Ordered Water Molecule in HIV-1 Protease
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Mycobacterium tuberculosis Serine/Threonine Protein Kinases
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RNA Polymerase II Transcription Elongation Control
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Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis
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Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR
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Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors
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Comprehensive review of targeted therapy for colorectal cancer
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“In the pathogenic milieu of AD, tau protein undergoes aberrant phosphorylation and then initiates a cascade of self-replicating protein aggregation that forms neurotoxic NFTs, resulting in neuronal injury and synaptic dysfunction [7].”
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TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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