Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications

Protein kinases are key mediators of cellular signaling and control cell functions through the phosphorylation of target proteins. They have become major targets for therapeutic agents aimed at treating human diseases, particularly cancer. Protein kinase inhibitors (PKIs) have emerged at the forefro...

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Main Authors: Salem Baldi, Nanbiao Long, Shu Ma, Li Liu, Abdullah Al-Danakh, Qin Yang, Xinpei Deng, Jindong Xie, Hailin Tang
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0747
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author Salem Baldi
Nanbiao Long
Shu Ma
Li Liu
Abdullah Al-Danakh
Qin Yang
Xinpei Deng
Jindong Xie
Hailin Tang
author_facet Salem Baldi
Nanbiao Long
Shu Ma
Li Liu
Abdullah Al-Danakh
Qin Yang
Xinpei Deng
Jindong Xie
Hailin Tang
author_sort Salem Baldi
collection DOAJ
description Protein kinases are key mediators of cellular signaling and control cell functions through the phosphorylation of target proteins. They have become major targets for therapeutic agents aimed at treating human diseases, particularly cancer. Protein kinase inhibitors (PKIs) have emerged at the forefront of drug development, and their investigations continue to be intense, with several candidates undergoing clinical trials and persistent endeavors to identify new chemical scaffolds. The main focus is still on developing isoform-selective compounds, which are inhibitors designed to target certain protein kinases, specifically isoforms, for more precise treatment. The identification and advancement of versatile inhibitor scaffolds that more effectively target individual kinases is essential for minimizing off-target effects and resistance. This review highlights important progress in PKI therapy, emphasizing the expansion of treatments for cancer, inflammatory diseases, and neurodegenerative diseases. Future efforts should focus on improving the specificity of inhibitors via mechanistic insights, developing combination therapies, establishing novel strategies, such as CRISPR-Cas9 integration with artificial intelligence-driven drug design, and overcoming resistance to enhance clinical treatment outcomes. Clinical case stories show the challenges and possible opportunities in this quickly evolving area.
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publisher American Association for the Advancement of Science (AAAS)
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spelling doaj-art-4c7e382e8cab42c8a69fe60f1f5863982025-08-20T02:37:17ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0747Advancements in Protein Kinase Inhibitors: From Discovery to Clinical ApplicationsSalem Baldi0Nanbiao Long1Shu Ma2Li Liu3Abdullah Al-Danakh4Qin Yang5Xinpei Deng6Jindong Xie7Hailin Tang8Department of Medical Laboratory Diagnostics, School of Medical Technology, Shaoyang University, Shaoyang 422000, China.Department of Medical Laboratory Diagnostics, School of Medical Technology, Shaoyang University, Shaoyang 422000, China.Department of Medical Laboratory Diagnostics, School of Medical Technology, Shaoyang University, Shaoyang 422000, China.Department of Medical Laboratory Diagnostics, School of Medical Technology, Shaoyang University, Shaoyang 422000, China.Department of Urology, First Affiliated Hospital, Dalian Medical University, Dalian, China.Centre for Biomedical Innovation and Technology, Puai Medical School, Shaoyang University, Shaoyang, China.State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.Protein kinases are key mediators of cellular signaling and control cell functions through the phosphorylation of target proteins. They have become major targets for therapeutic agents aimed at treating human diseases, particularly cancer. Protein kinase inhibitors (PKIs) have emerged at the forefront of drug development, and their investigations continue to be intense, with several candidates undergoing clinical trials and persistent endeavors to identify new chemical scaffolds. The main focus is still on developing isoform-selective compounds, which are inhibitors designed to target certain protein kinases, specifically isoforms, for more precise treatment. The identification and advancement of versatile inhibitor scaffolds that more effectively target individual kinases is essential for minimizing off-target effects and resistance. This review highlights important progress in PKI therapy, emphasizing the expansion of treatments for cancer, inflammatory diseases, and neurodegenerative diseases. Future efforts should focus on improving the specificity of inhibitors via mechanistic insights, developing combination therapies, establishing novel strategies, such as CRISPR-Cas9 integration with artificial intelligence-driven drug design, and overcoming resistance to enhance clinical treatment outcomes. Clinical case stories show the challenges and possible opportunities in this quickly evolving area.https://spj.science.org/doi/10.34133/research.0747
spellingShingle Salem Baldi
Nanbiao Long
Shu Ma
Li Liu
Abdullah Al-Danakh
Qin Yang
Xinpei Deng
Jindong Xie
Hailin Tang
Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
Research
title Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
title_full Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
title_fullStr Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
title_full_unstemmed Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
title_short Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications
title_sort advancements in protein kinase inhibitors from discovery to clinical applications
url https://spj.science.org/doi/10.34133/research.0747
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