دورية أكاديمية
An integrative epigenome-based strategy for unbiased functional profiling of clinical kinase inhibitors
العنوان: | An integrative epigenome-based strategy for unbiased functional profiling of clinical kinase inhibitors |
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المؤلفون: | Francesco Gualdrini, Stefano Rizzieri, Sara Polletti, Francesco Pileri, Yinxiu Zhan, Alessandro Cuomo, Gioacchino Natoli |
المصدر: | Molecular Systems Biology, Vol 20, Iss 6, Pp 626-650 (2024) |
بيانات النشر: | Springer Nature, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Biology (General) LCC:Medicine (General) |
مصطلحات موضوعية: | Clinical Kinase Inhibitors, Inflammation, Machine Learning, Epigenome, Drug Repurposing, Biology (General), QH301-705.5, Medicine (General), R5-920 |
الوصف: | Abstract More than 500 kinases are implicated in the control of most cellular process in mammals, and deregulation of their activity is linked to cancer and inflammatory disorders. 80 clinical kinase inhibitors (CKIs) have been approved for clinical use and hundreds are in various stages of development. However, CKIs inhibit other kinases in addition to the intended target(s), causing both enhanced clinical effects and undesired side effects that are only partially predictable based on in vitro selectivity profiling. Here, we report an integrative approach grounded on the use of chromatin modifications as unbiased, information-rich readouts of the functional effects of CKIs on macrophage activation. This approach exceeded the performance of transcriptome-based approaches and allowed us to identify similarities and differences among CKIs with identical intended targets, to recognize novel CKI specificities and to pinpoint CKIs that may be repurposed to control inflammation, thus supporting the utility of this strategy to improve selection and use of CKIs in clinical settings. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1744-4292 |
Relation: | https://doaj.org/toc/1744-4292 |
DOI: | 10.1038/s44320-024-00040-x |
URL الوصول: | https://doaj.org/article/cd91a4c67fc642fc9f116b3fb517bb40 |
رقم الأكسشن: | edsdoj.91a4c67fc642fc9f116b3fb517bb40 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 17444292 |
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DOI: | 10.1038/s44320-024-00040-x |