A membrane permeability database for nonpeptidic macrocycles
Abstract The process of developing new drugs is arduous and costly, particularly for targets classified as “difficult-to-drug.” Macrocycles show a particular ability to modulate difficult-to-drug targets, including protein-protein interactions, while still allowing oral administration. However, the...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Scientific Data |
| Online Access: | https://doi.org/10.1038/s41597-024-04302-z |
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| Summary: | Abstract The process of developing new drugs is arduous and costly, particularly for targets classified as “difficult-to-drug.” Macrocycles show a particular ability to modulate difficult-to-drug targets, including protein-protein interactions, while still allowing oral administration. However, the determination of membrane permeability, critical for reaching intracellular targets and for oral bioavailability, is laborious and expensive. In silico methods are a cost-effective alternative, enabling predictions prior to compound synthesis. Here, we present a comprehensive online database ( https://swemacrocycledb.com/ ), housing 5638 membrane permeability datapoints for 4216 nonpeptidic macrocycles, curated from the literature, patents, and bioactivity repositories. In addition, we present a new descriptor, the “amide ratio” (AR), that quantifies the peptidic nature of macrocyclic compounds, enabling the classification of peptidic, semipeptidic, and nonpeptidic macrocycles. Overall, this resource fills a gap among existing databases, offering valuable insights into the membrane permeability of nonpeptidic and semipeptidic macrocycles, and facilitating predictions for drug discovery projects. |
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| ISSN: | 2052-4463 |