Profiling disease-selective drug targets: from proteomics to ligandomics.
Profiling disease-selective drug targets: from proteomics to ligandomics.
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DOI：
10.1016/j.drudis.2022.103430
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发表时间：
2022-11
影响因子：
7.4
通讯作者：
Prabuddha Waduge;H. Tian;K. Webster;Wei Li
中科院分区：
文献类型：
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作者：
Prabuddha Waduge;H. Tian;K. Webster;Wei Li
亮点细胞配体是最有价值的药物靶点之一。传统上，它们是根据具体情况进行识别的，存在技术挑战。配体组学系统地绘制了细胞配体和疾病限制性配体。四种验证测定法可评估已识别药物靶点的质量。Scg3 被发现是抗血管生成治疗的疾病限制性靶点。尽管包括蛋白质组学和转录组学在内的组学技术取得了进步，但治疗靶点的识别仍然具有挑战性。配体组学最近作为一种独特的功能蛋白质组学技术出现，用于细胞结合蛋白配体的全局分析。当应用于患病与健康脉管系统时，比较配体组学系统地绘制了新型疾病限制性配体，这些配体允许选择性靶向病理而非生理途径，从而提供高效和本质安全性。在这篇综述中，我们讨论了细胞配体作为治疗靶点的潜力，并总结了配体组学的发展。我们进一步比较了不同组学技术在药物靶点发现方面的优势和局限性，并讨论了靶点选择标准，以提高药物研发的成功率。
HighlightsCellular ligands are among the most valuable drug targets.They are traditionally identified on a case-by-case basis with technical challenges.Ligandomics systematically maps cellular ligands and disease-restricted ligands.Four validation assays to evaluate the quality of identified drug targets.Scg3 was discovered as a disease-restricted target for anti-angiogenic therapy.Despite advancements in omics technologies, including proteomics and transcriptomics, identification of therapeutic targets remains challenging. Ligandomics recently emerged as a unique technology of functional proteomics for global profiling of cell-binding protein ligands. When applied to diseased versus healthy vasculatures, comparative ligandomics systematically maps novel disease-restricted ligands that allow selective targeting of pathological but not physiological pathways, providing high efficacy with intrinsic safety. In this review, we discuss the potential of cellular ligands as therapeutic targets and summarize the development of ligandomics. We further compare the advantages and limitations of different omics technologies for drug target discovery and discuss target selection criteria to improve drug R&D success rates.