Advances in Nuclear Magnetic Resonance for Drug Discovery.
Advances in Nuclear Magnetic Resonance for Drug Discovery.
复制标题
核磁共振在药物发现方面的进展。
DOI：
10.1517/17460440903232623
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发表时间：
2009-10-01
影响因子：
6.3
通讯作者：
Powers R
中科院分区：
文献类型：
--
作者：
Powers R
药物发现是一项复杂且不可预测的工作，失败率很高。制药行业当前的趋势加剧了这些挑战，并导致过去十年生产力急剧下降。通过迫使药物发现过程遵守装配线协议来实现科学工业化，这施加了不必要的限制，例如较短的项目时间表。核磁共振的最新进展正在应对这些自身限制，并为提高药物发现的成功率提供了机会。将回顾核磁共振技术的最新进展，这些技术有可能显着影响和有益于药物发现过程。其中包括快速 NMR 数据收集方案和高通量蛋白质结构测定、快速蛋白质-配体共结构测定、使用基于片段的 NMR 亲和筛选发现先导化合物、监测先导化合物体内功效和毒性的 NMR 代谢组学，以及通过 FAST-NMR 对蛋白质进行功能注释来鉴定新的治疗靶点。 NMR 是药物发现过程的关键组成部分，该技术的多功能性使其能够不断扩展和发展其作用。随着自动化、结构计算速度、细胞内成像技术以及 NMR 适合目标的扩展的进步，NMR 预计将在未来十年保持这种增长。
Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets.
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影响因子：
3.4
作者：
Caldwell, Gary W.;Ritchie, David M.;Yan, Zhengyin
通讯作者：
Yan, Zhengyin
影响因子：
15
作者：
Coggins, BE;Venters, RA;Zhou, P
通讯作者：
Zhou, P
影响因子：
7.8
作者：
Cooke, RM
通讯作者：
Cooke, RM
影响因子：
3.7
作者：
Andrews, CW;Bennett, L;Yu, LX
通讯作者：
Yu, LX
影响因子：
56.9
作者：
Boehr, David D.;McElheny, Dan;Wright, Peter E.
通讯作者：
Wright, Peter E.