Network biology as a new approach to drug discovery.

John A Lowe, Phil Jones, David M Wilson
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Abstract

The decline in productivity of the pharmaceutical industry may stem, at least in part, from underestimating the complexity of human disease. While a disease-relevant gene or protein may initially seem to be an attractive drug target, appreciating its role in the network of pathways involved in a disease provides a better perspective for making this decision. In some cases, off-target effects or redundancy in the network can negate the potential efficacy of a new drug. Even a successful drug, such as imatinib (Gleevec), may be less selective than originally thought, resulting in important, and sometimes useful, consequences. Advances in the area of network biology provide an important perspective on the potential of a drug target, and are being applied to various diseases. The impact of these advances on the field of drug discovery is assessed.

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网络生物学作为药物发现的新途径。
制药业生产率的下降可能至少部分源于低估了人类疾病的复杂性。虽然疾病相关基因或蛋白质最初可能看起来是一个有吸引力的药物靶点,但了解其在疾病通路网络中的作用可以为做出这一决定提供更好的视角。在某些情况下,网络中的脱靶效应或冗余可能会抵消新药的潜在功效。即使是一种成功的药物,如伊马替尼(格列卫),也可能比最初想象的选择性更低,从而导致重要的,有时是有用的后果。网络生物学领域的进展为研究药物靶点的潜力提供了一个重要的视角,并正在应用于各种疾病。评估了这些进展对药物发现领域的影响。
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The role of the mTOR pathway in regulating food intake. The role of tau kinases in Alzheimer's disease. Current understanding and importance of histone phosphorylation in regulating chromatin biology. Network biology as a new approach to drug discovery. Conformational ensembles, signal transduction and residue hot spots: application to drug discovery.
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