The art of finding the right drug target: emerging methods and strategies

The art of finding the right drug target: emerging methods and strategies

12 June 2024 | Zi-Chang Jia, Xue Yang, Yi-Kun Wu, Min Li, Debatosh Das, Mo-Xian Chen, Jian Wu
The article "The Art of Finding the Right Drug Target: Emerging Methods and Strategies" by Zi-Chang Jia, Xue Yang, Yi-Kun Wu, Min Li, Debatosh Das, Mo-Xian Chen, and Jian Wu, provides a comprehensive overview of emerging drug target discovery methods. The authors highlight the significance of drug target discovery in the development of new drugs, particularly in cancer therapy and precision medicine. Traditional methods are time-consuming and costly, leading to the development of modern techniques that enhance efficiency and reduce costs. The article is divided into several sections, including an introduction, the emergence of new drug target discovery methods, applications in human disease treatment, and a conclusion. Key methods discussed include: 1. **Drug-Centric Target Discovery Methods**: - **Drug Affinity Responsive Target Stability (DARTS)**: This method monitors changes in protein stability by observing the protection of target proteins from degradation by ligands. - **Network-Based and Machine Learning Methods**: These approaches use bioinformatics networks and machine learning algorithms to predict drug targets based on known interactions and molecular features. 2. **Disease-Centric Target Discovery Methods**: - **Gene Targeting Approaches**: Techniques like CRISPR-Cas9, RNA interference, and zinc-finger nucleases are used to modify specific genes to understand their roles in disease pathways. - **Posttranscriptional Regulation-Based Discovery**: Nonsense-mediated mRNA decay (NMD) is utilized to identify targets by monitoring mRNA degradation and its impact on protein production. - **Multi-Omics Approach**: Integrating data from proteomics, genomics, metabolomics, transcriptomics, and phenomics to uncover disease-specific biomarkers and potential drug targets. 3. **Applications in Human Disease Treatment**: - **Practical Applications of Drug-Centric Methods**: Examples include the use of DARTS to identify therapeutic targets for various cancers and the application of network-based and machine learning methods in breast cancer and COVID-19 research. - **Practical Applications of Disease-Centric Methods**: CRISPR library screening has been used to identify targets in cancers, neurodegenerative diseases, and other conditions. - **Multimethod Combinations**: Combining multiple methods, such as multi-omics with CRISPR/Cas9 screening, enhances the reliability and comprehensiveness of target discovery. The article concludes by emphasizing the importance of combining multiple methods and leveraging large databases to accelerate drug discovery and improve therapeutic outcomes. It also highlights the role of computational and experimental methods in reducing costs and increasing the success rate of drug development.The article "The Art of Finding the Right Drug Target: Emerging Methods and Strategies" by Zi-Chang Jia, Xue Yang, Yi-Kun Wu, Min Li, Debatosh Das, Mo-Xian Chen, and Jian Wu, provides a comprehensive overview of emerging drug target discovery methods. The authors highlight the significance of drug target discovery in the development of new drugs, particularly in cancer therapy and precision medicine. Traditional methods are time-consuming and costly, leading to the development of modern techniques that enhance efficiency and reduce costs. The article is divided into several sections, including an introduction, the emergence of new drug target discovery methods, applications in human disease treatment, and a conclusion. Key methods discussed include: 1. **Drug-Centric Target Discovery Methods**: - **Drug Affinity Responsive Target Stability (DARTS)**: This method monitors changes in protein stability by observing the protection of target proteins from degradation by ligands. - **Network-Based and Machine Learning Methods**: These approaches use bioinformatics networks and machine learning algorithms to predict drug targets based on known interactions and molecular features. 2. **Disease-Centric Target Discovery Methods**: - **Gene Targeting Approaches**: Techniques like CRISPR-Cas9, RNA interference, and zinc-finger nucleases are used to modify specific genes to understand their roles in disease pathways. - **Posttranscriptional Regulation-Based Discovery**: Nonsense-mediated mRNA decay (NMD) is utilized to identify targets by monitoring mRNA degradation and its impact on protein production. - **Multi-Omics Approach**: Integrating data from proteomics, genomics, metabolomics, transcriptomics, and phenomics to uncover disease-specific biomarkers and potential drug targets. 3. **Applications in Human Disease Treatment**: - **Practical Applications of Drug-Centric Methods**: Examples include the use of DARTS to identify therapeutic targets for various cancers and the application of network-based and machine learning methods in breast cancer and COVID-19 research. - **Practical Applications of Disease-Centric Methods**: CRISPR library screening has been used to identify targets in cancers, neurodegenerative diseases, and other conditions. - **Multimethod Combinations**: Combining multiple methods, such as multi-omics with CRISPR/Cas9 screening, enhances the reliability and comprehensiveness of target discovery. The article concludes by emphasizing the importance of combining multiple methods and leveraging large databases to accelerate drug discovery and improve therapeutic outcomes. It also highlights the role of computational and experimental methods in reducing costs and increasing the success rate of drug development.
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