期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 41, 期 5, 页码 305-317出版社
CELL PRESS
DOI: 10.1016/j.tips.2020.02.006
关键词
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资金
- Linde Program in Cancer Chemical Biology
- NCI [T32 CA236754]
Small molecules continue to dominate drug discovery because of their ease of use, lower cost of manufacturing, and access to intracellular targets. However, despite these advantages, small molecules are more likely to fail in clinical trials compared with biologicals and their development remains limited to a small subset of disease-relevant 'druggable' targets. Targeted protein degradation has recently emerged as a novel pharmacological modality that promises to overcome small molecule limitations whilst retaining their key advantages. Here, we use a Strengths-Weaknesses-Opportunities-Threats (SWOT) framework to critically assess the current status of this rapidly evolving field. We expect that degrader molecules are only the beginning of a range of novel targeting modalities that hijack existing endogenous cellular machineries to chemically redirect biological targets and pathways. Therefore, this piece may offer a roadmap for enhancing development of both degraders and related modalities.
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