期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 44, 页码 15584-15594出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201906284
关键词
chemical biology; drug delivery; drug design; organelle targeting; subcellular distribution
资金
- Israel Science Foundation [6/14]
The ratio between the dose of drug required for optimal efficacy and the dose that causes toxicity is referred to as the therapeutic window. This ratio can be increased by directing the drug to the diseased tissue or pathogenic cell. For drugs targeting fungi and malignant cells, the therapeutic window can be further improved by increasing the resolution of drug delivery to the specific organelle that harbors the drug's target. Organelle targeting is challenging and is, therefore, an under-exploited strategy. Here we provide an overview of recent advances in control of the subcellular distribution of small molecules with the focus on chemical modifications. Highlighted are recent examples of active and passive organelle-specific targeting by incorporation of organelle-directing molecular determinants or by chemical modifications of the pharmacophore. The outstanding potential that lies in the development of organelle-specific drugs is becoming increasingly apparent.
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