Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 62, Issue 20, Pages 8881-8914Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.9b00017
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Funding
- National Natural Science Foundation of China [81573281, 81830105]
- Double First-Class initiative innovation team project of China Pharmaceutical University [CPU2018GF11, CPU2018GY34]
- Joint Laboratory of China Pharmaceutical University
- Taian City Central Hospital
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Due to the complexity of multifactorial diseases, single-target drugs do not always exhibit satisfactory efficacy. Recently, increasing evidence indicates that simultaneous modulation of multiple targets may improve both therapeutic safety and efficacy, compared with single-target drugs. However, few multitarget drugs are on market or in clinical trials, despite the best efforts of medicinal chemists. This article discusses the systematic establishment of target combination, lead generation, and optimization of multitarget-directed ligands (MTDLs). Moreover, we analyze some MTDLs research cases for several complex diseases in recent years and the physicochemical properties of 117 clinical multitarget drugs, with the aim to reveal the trends and insights of the potential use of MTDLs.
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