小分子化学“探针”与分子生物学技术相辅相成, 可用于探索、验证和生成关于蛋白质在癌症等疾病中的功能的假设。不幸的是, 选择和使用小分子试剂不当可能导致错误的结论。在此, 我们提供了使用不良化学工具的例子, 并为癌症研究中高质量化学探针的选择、验证和使用提供了最佳实践建议。我们还要提到与新型药物模态相关的工具的复杂性, 如蛋白降解剂, 并提供建议和资源, 以便研究人员能够独立确认合适的小分子探针。对生物学靶点和通路的验证将受益于对使这项工作成为可能的小分子试剂（“化学探针”）的效力、选择性和靶点结合相关标准的共享理解。癌症生物学家、药物化学家和化学生物学家之间的跨学科合作以及对可用资源的认识将减少误导性数据的生成和解释, 增强数据的可靠性, 提高学术和工业研究的生产力。©2023 American Association for Cancer Research.

Small-molecule chemical "probes" complement the use of molecular biology techniques to explore, validate, and generate hypotheses on the function of proteins in diseases such as cancer. Unfortunately, the poor selection and use of small-molecule reagents can lead to incorrect conclusions. Here, we illustrate examples of poor chemical tools and suggest best practices for the selection, validation, and use of high-quality chemical probes in cancer research. We also note the complexity associated with tools for novel drug modalities, exemplified by protein degraders, and provide advice and resources to facilitate the independent identification of appropriate small-molecule probes by researchers.Validation of biological targets and pathways will be aided by a shared understanding of the criteria of potency, selectivity, and target engagement associated with small-molecule reagents ("chemical probes") that enable that work. Interdisciplinary collaboration between cancer biologists, medicinal chemists, and chemical biologists and the awareness of available resources will reduce misleading data generation and interpretation, strengthen data robustness, and improve productivity in academic and industrial research.©2023 American Association for Cancer Research.