Exploring DrugCentral: from molecular structures to clinical effects

Area of Science:

• Pharmacology and Cheminformatics
• Drug Discovery and Development
• Computational Biology

Background:

• DrugCentral is an open-access online repository providing extensive drug information.
• It integrates structural, physicochemical, and pharmacological data for over 4950 drugs.
• The platform includes bioactivity data, mechanism-of-action targets, and clinical information.

Purpose of the Study:

• To present DrugCentral as a versatile resource for drug discovery, development, and repositioning.
• To demonstrate a use-case for drug repurposing using DrugCentral's experimentally determined data.
• To introduce a drug repurposing classification scheme considering intellectual property and market factors.

Main Methods:

• Data aggregation from multiple digital sources with manual curation.
• Analysis of bioactivity data for human mechanism-of-action targets to establish activity thresholds.
• Development of a drug repurposing classification scheme incorporating intellectual property and market accessibility.

Main Results:

• DrugCentral contains data on >4950 drugs, ~20,000 bioactivity points, 724 MoA targets, >14,300 uses, 27,000 contraindications, and ~340,000 adverse events.
• A general activity threshold (t = 6, or 1 µM) was suggested for repurposing 87% of drugs against novel targets.
• A refined threshold (t = 3 - logS) based on water solubility was proposed for logS < -3.

Conclusions:

• DrugCentral serves as a comprehensive pharmaceutical reference, facilitating drug discovery and repositioning.
• The established activity thresholds and refined empirical formula aid in prioritizing drug repurposing candidates.
• The integrated classification scheme enhances the efficiency of drug repurposing programs by considering commercial viability.