CoDReS

CoDReS prioritizes candidate drugs for repurposing by integrating transcriptomic profile changes, common targets, and structural similarity with functional and structural drugability scoring to rank compounds for further validation.

Key Features:

• Integrated Drug Ranking: Combines an initial repurposing score derived from transcriptomic modulation, common targets, and structural similarities with additional evaluation layers to produce a composite ranking.
• Functional Score Assessment: Evaluates each candidate's potential to address disease-implicated biological pathways via a functional relevance score.
• Structural Score Evaluation: Computes a structural score to identify drugability violations and filter structurally unfavorable compounds.
• Structural Similarity Clustering: Clusters drugs by structural similarity and selects representative structural exemplars for further in vitro and in vivo validation.
• Filtering Based on Clinical Trial Data: Refines results by comparing structural similarity to drugs that failed in clinical trials against the disease to avoid redundant testing.

Scientific Applications:

• Drug repurposing prioritization: Ranks existing drugs for new therapeutic indications using transcriptomic, target and structural evidence.
• Pre-clinical and clinical candidate selection: Identifies exemplar compounds for in vitro and in vivo validation and supports decision-making in pre-clinical and clinical research phases.
• Redundant-testing reduction: Filters out candidates structurally similar to prior clinical-trial failures to focus efforts on more promising compounds.

Methodology:

Initial scoring based on potential to modify transcriptomic profiles or via common targets and structural similarities; functional relevance assessment; structural scoring to detect drugability violations; structural similarity clustering with exemplar selection; result filtering by structural similarity to compounds that failed in clinical trials.