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Phenotypic drug discovery: a case for thymosin alpha-1
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses thymosin alpha-1, a thymic peptide hormone, within the framework of phenotypic drug discovery (PDD), an approach that screens compounds for their effects on cells, tissues, or whole organisms (species not specified) without requiring prior knowledge of a specific molecular target. The authors contrast PDD with target-based drug discovery strategies and describe its potential to address the complexity of human disease, including interactions between multiple metabolites, targets, and the host-microbe metabolic network. The review discusses challenges in PDD, such as hit validation and target deconvolution, and reviews researchers' experience testing thymosin alpha-1 in preclinical and clinical settings, discussing how the PDD framework might accommodate its therapeutic use in precision medicine.
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.
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