化学
药品
计算生物学
连接器
药物输送
药物发现
靶向给药
配体(生物化学)
药理学
纳米技术
受体
医学
生物化学
计算机科学
生物
操作系统
有机化学
材料科学
作者
Madduri Srinivasarao,Philip S. Low
出处
期刊:Chemical Reviews
[American Chemical Society]
日期:2017-09-12
卷期号:117 (19): 12133-12164
被引量:445
标识
DOI:10.1021/acs.chemrev.7b00013
摘要
Safety and efficacy constitute the major criteria governing regulatory approval of any new drug. The best method to maximize safety and efficacy is to deliver a proven therapeutic agent with a targeting ligand that exhibits little affinity for healthy cells but high affinity for pathologic cells. The probability of regulatory approval can conceivably be further enhanced by exploiting the same targeting ligand, conjugated to an imaging agent, to select patients whose diseased tissues display sufficient targeted receptors for therapeutic efficacy. The focus of this Review is to summarize criteria that must be met during design of ligand-targeted drugs (LTDs) to achieve the required therapeutic potency with minimal toxicity. Because most LTDs are composed of a targeting ligand (e.g., organic molecule, aptamer, protein scaffold, or antibody), spacer, cleavable linker, and therapeutic warhead, criteria for successful design of each component will be described. Moreover, because obstacles to successful drug design can differ among human pathologies, limitations to drug delivery imposed by the unique characteristics of different diseases will be considered. With the explosion of genomic and transcriptomic data providing an ever-expanding selection of disease-specific targets, and with tools for high-throughput chemistry offering an escalating diversity of warheads, opportunities for innovating safe and effective LTDs has never been greater.
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