New Modalities, Technologies, and Partnerships in Probe and Lead Generation: Enabling a Mode-of-Action Centric Paradigm
New Modalities, Technologies, and Partnerships in Probe and Lead Generation: Enabling a Mode-of-Action Centric Paradigm
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DOI：
10.1021/acs.jmedchem.8b00378
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发表时间：
2018-10-25
影响因子：
7.3
通讯作者：
Jimonet，Patrick
中科院分区：
文献类型：
--
作者：
Valeur，Eric;Jimonet，Patrick
随着新生物学和源于基因组学进步的高潜力靶标识别技术的兴起，药物化学家正逐渐面临越来越复杂的目标，而且往往是前所未有的。新的命中查找技术与更广泛的药物模式选择相结合，产生了一系列独特的选择，以应对这些具有挑战性的目标并确定合适的优化起点。此外，源自一系列学术团体和生物技术公司的创新解决方案需要新型的合作模式，以在药物发现过程中利用和整合它们。这一观点为药物化学家提供了一个指南，涵盖了当代的探测和引线产生方法，并讨论了每种策略的优点和局限性。此外，调节蛋白质的策略的扩展创造了一种不可知的、以行动模式为中心的命中发现范式的机会。
With the rise of novel biology and high potential target identification technologies originating from advances in genomics, medicinal chemists are progressively facing targets of increasing complexity and often unprecedented. Novel hit finding technologies, combined with a wider choice of drug modalities, has resulted in a unique repertoire of options to address these challenging targets and to identify suitable starting points for optimization. Furthermore, innovative solutions originating from a range of academic groups and biotech companies require new types of collaborative models to leverage and integrate them in the drug discovery process. This perspective provides a guide for medicinal chemists covering contemporary probe and lead generation approaches and discusses the strengths and limitations of each strategy. Moreover, the expansion of strategies to modulate proteins creates the opportunity of a modality-agnostic and mode-of-action centric hit finding paradigm.