The target landscape of clinical kinase drugs
Open accessAbstract
An atlas for drug interactions: Kinase inhibitors are an important class of drugs that block certain enzymes involved in diseases such as cancer and inflammatory disorders. There are hundreds of kinases within the human body, so knowing the kinase “target” of each drug is essential for developing successful treatment strategies. Sometimes clinical trials can fail because drugs bind more than one target. Yet sometimes off-target effects can be beneficial, and drugs can be repurposed for treatment of additional diseases. Klaeger et al. performed a comprehensive analysis of 243 kinase inhibitors that are either approved for use or in clinical trials. They provide an open-access resource of target summaries that could help researchers develop better drugs, understand how existing drugs work, and design more effective clinical trials. Science , this issue p. eaan4368
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Over the years, a vast number of small molecule kinase inhibitors have been developed that exhibit significant clinical benefits.
“Over the years, a vast number of small molecule kinase inhibitors have been developed that exhibit significant clinical benefits (Klaeger et al. 2017).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Klaeger et al. 2017
The Abstract calls kinase inhibitors important cancer therapeutics and reports 37 approved drugs and more than 250 in clinical trials. This supports the development of many inhibitors and the clinical value of approved drugs, but it does not establish that the much larger group in trials exhibits significant clinical benefits. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe model implements more drug targets than reported by Klaeger et al. (2017).
“The model implements more drug targets than what is reported by Klaeger et al. (2017), who did not measure affinities for, e.g., multiple members of the ERBB-family.”
From Efficient Parameter Estimation Enables the Prediction of Drug Response Using a Mechanistic Pan-Cancer Pathway Model (2018) · cites this paper as Klaeger et al., 2017
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 [6]
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Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs
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Self-citationExome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia
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Analysis of Kinase Inhibitor Selectivity using a Thermodynamics-Based Partition Index
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The importance of Src signaling in sarcoma
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OTSSP167 Abrogates Mitotic Checkpoint through Inhibiting Multiple Mitotic Kinases
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Self-citationA theoretical entropy score as a single value to express inhibitor selectivity
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What general conclusions can we draw from kinase profiling data sets?
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Self-citationProtein kinase networks that limit TLR signalling
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Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127
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Self-citation
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Kinase inhibitors: the road ahead
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Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development
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Targeting dementias through cancer kinases inhibition
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“Over the years, a vast number of small molecule kinase inhibitors have been developed that exhibit significant clinical benefits (Klaeger et al. 2017).”
InfluentialPersonalized precision medicine
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- Authors
- Klaeger, S., Heinzlmeir, S., Wilhelm, M., Polzer, H., Vick, B., Koenig, P.-A., Reinecke, M., Ruprecht, B., Petzoldt, S., Meng, C., Zecha, J., Reiter, K., Qiao, H., Helm, D., Koch, H., Schoof, M., Canevari, G., Casale, E., Depaolini, S. R., Feuchtinger, A., Wu, Z., Schmidt, T., Rueckert, L., Becker, W., Huenges, J., Garz, A.-K., Gohlke, B.-O., Zolg, D. P., Kayser, G., Vooder, T., Preissner, R., Hahne, H., Tõnisson, N., Kramer, K., Götze, K., Bassermann, F., Schlegl, J., Ehrlich, H.-C., Aiche, S., Walch, A., Greif, P. A., Schneider, S., Felder, E. R., Ruland, J., Médard, G., Jeremias, I., Spiekermann, K., & Kuster, B.
- Affiliations
- German Cancer Research Center (DE)
- Technical University of Munich (DE)
- Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), Freising, Germany.
- Nerviano Medical Sciences (IT)
- Helmholtz Munich (DE)
- Systems, Applications & Products in Data Processing (Germany) (DE)
- German Cancer Consortium (DKTK), Heidelberg, Germany.
- University of Freiburg (DE)
- Center of Thoracic Surgery, Krefeld, Germany.
- Tartu University Hospital (EE)
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Klaeger, Susan
- Heinzlmeir, Stephanie
- Wilhelm, Mathias
- ORCID
- Klaeger, Susan
- Heinzlmeir, Stephanie
- Wilhelm, Mathias
- Vick, Binje
- Koenig, Paul-Albert
- Reinecke, Maria
- Ruprecht, Benjamin
- Meng, Chen
- Zecha, Jana
- Reiter, Katrin
- Helm, Dominic
- Schoof, Melanie
- Feuchtinger, Annette
- Wu, Zhixiang
- Schmidt, Tobias
- Becker, Wilhelm
- Gohlke, Bjoern-Oliver
- Zolg, Daniel Paul
- Kayser, Gian
- Vooder, Tonu
- Preissner, Robert
- Hahne, Hannes
- Tõnisson, Neeme
- Kramer, Karl
- Götze, Katharina
- Bassermann, Florian
- Schlegl, Judith
- Ehrlich, Hans-Christian
- Aiche, Stephan
- Walch, Axel
- Greif, Philipp A.
- Schneider, Sabine
- Felder, Eduard Rudolf
- Ruland, Juergen
- Médard, Guillaume
- Jeremias, Irmela
- Spiekermann, Karsten
- Kuster, Bernhard
- Venue
- Science
- Published
- 2017-12
- Volume
- 358
- Issue
- 6367
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6542668
- OpenAlex
- W2773242491
- Cited by
- 854
- References
- 126
- Citations by year
- 2026: 79 · 2025: 85 · 2024: 86 · 2023: 103 · 2022: 89 · 2021: 122 · 2020: 109 · 2019: 105 · 2018: 72 · 2017: 3
- FWCI
- 60.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- kinase inhibitors, chemoproteomics, off-target effects, phosphoproteomics, combination therapy, MELK, cabozantinib, FLT3-ITD acute myeloid leukemia, lung cancer, drug repurposing
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Lung Neoplasms, Leukemia, Myeloid, Acute, Cytokines, Protein Serine-Threonine Kinases, Xenograft Model Antitumor Assays, Proteomics, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, fms-Like Tyrosine Kinase 3, Drug Discovery, Molecular Targeted Therapy
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