New Database Accelerates Design of Hard-to-Treat Drug Candidates
Researchers have published a database of over 5,600 membrane permeability measurements for ring-shaped drug molecules, enabling computational predictions that could slash development costs. The resource addresses a major bottleneck in creating medicines targeting previously undruggable disease mechanisms, potentially shortening timelines for biotech and pharma companies.
Originaltitel: A membrane permeability database for nonpeptidic macrocycles
<p>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.</p>