DrugReason: Dynamic Multi-View Reasoning over Knowledge Graph and Language Evidence for Drug Repurposing

Abstract

Drug repurposing aims to identify new therapeutic uses for existing compounds and, compared with de novo drug discovery, offers a faster and more cost-effective path to clinical translation. However, the space of candidate drug-disease pairs is enormous and their underlying relationships often depend on complex multi-hop biological mechanisms, making it difficult to reliably predict which pairs represent true therapeutic relationships. Existing approaches tackle this from two directions: knowledge graph-based methods organize curated biomedical evidence into structured relational networks for grounded multi-hop reasoning, while LLM-based methods leverage pretrained knowledge to generate flexible mechanistic rationales. Yet neither is sufficient alone - KGs are confined to observed graph structure while LLMs lack factual grounding and risk hallucination. To address this gap, we propose DrugReason, a multi-view reasoning framework that integrates grounded KG reasoning with LLM-generated mechanistic inference for drug repurposing. DrugReason adaptively routes diverse reasoning paths to specialized experts conditioned on the query context, while a cross-expert distillation objective enables knowledge sharing without sacrificing expert specialization. Experiments on PharmaDB, DDInter, and DrugBank show that DrugReason improves average performance over strong single-view reasoning baselines and achieves competitive or superior results compared with graph-based alternatives, while providing interpretable routing-based predictions.