Guiding Drugs to Target-Harboring Organelles: Stretching Drug-Delivery to a Higher Level of Resolution.

Autor: Louzoun-Zada S; School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel., Jaber QZ; School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel., Fridman M; School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2019 Oct 28; Vol. 58 (44), pp. 15584-15594. Date of Electronic Publication: 2019 Aug 12.
DOI: 10.1002/anie.201906284
Abstrakt: 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.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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