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Abstract：
Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host-microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework.
摘要：
表型药物发现（PDD）涉及筛选化合物对细胞的影响，组织，或整个生物体不一定了解潜在的分子靶标。PDD与基于靶标的策略不同，因为它不需要了解特定的药物靶标或其在疾病中的作用。这种方法可以导致发现具有意想不到的治疗效果或应用的药物，并允许根据其功能效果来鉴定药物，而不是通过预定义的基于目标的方法。最终,疾病的定义主要是基于症状，而不是基于机制，治疗方法也应该如此。近年来,人们对PDD重新产生了兴趣，因为它有可能解决人类疾病的复杂性，包括与构成代谢宿主-微生物相互作用中心中心的多个靶标的多种代谢物的整体图景。尽管PDD提出了诸如命中验证和目标反卷积等挑战，大数据时代取得了重大成就。本文探讨了研究人员测试胸腺肽激素作用的经验，胸腺素α-1，在临床前和临床环境中，并讨论其在精准医学时代的治疗效用如何在PDD框架内适应。
