Computational and Practical Aspects of Drug Repositioning

Area of Science:

• Pharmacology
• Drug Discovery
• Translational Medicine

Background:

• Hypothesis-driven drug repurposing presents advantages like reduced costs, higher success rates, and near-term clinical potential.
• Advancements in computing and databases facilitate hypothesis generation for drug repurposing, rescue, and repositioning.
• The approach is particularly valuable for rare, orphan, and under-researched diseases, offering a lower barrier to entry compared to de novo drug discovery.

Purpose of the Study:

• To address underdeveloped aspects and define clearer standards for hypothesis-driven drug repurposing research.
• To introduce a novel classification scheme, the Drug Repositioning Evidence Level (DREL), for evaluating scientific evidence in drug repositioning.
• To present concepts for rapid and effective filtering of drug repurposing hypotheses to prioritize safe and practical applications.

Main Methods:

• Development of the Drug Repositioning Evidence Level (DREL) classification scheme, ranging from DREL 0 (no experimental support) to DREL 4 (approved for new indication).
• Discussion of factors influencing the evaluation of drug repurposing projects.
• Identification and discussion of promising drug repurposing leads for specific diseases.

Main Results:

• Proposal of the DREL scale to standardize the assessment of evidence supporting drug repositioning efforts.
• Presentation of a framework for hypothesis filtering to identify viable drug repurposing candidates.
• Identification of potential drug repurposing candidates for malaria (DREL-1) and amoebic dysentery (DREL-2).

Conclusions:

• The proposed DREL system provides a standardized method for classifying drug repositioning projects based on scientific evidence.
• Effective hypothesis filtering is crucial for focusing on drug repurposing strategies with the highest potential for safe and practical clinical application.
• The study highlights promising avenues for drug repurposing in neglected diseases like malaria and amoebic dysentery.