HCDT 2.0: A Highly Confident Drug-Target Database for Experimentally Validated Genes, RNAs, and Pathways.

Drug-target interactions constitute the fundamental basis for understanding drug action mechanisms and advancing therapeutic discovery. While existing drug-target databases have contributed valuable resources, they exhibit structural and functional fragmentation due to heterogeneous data sources and annotation standards. Building upon the high-confidence drug-gene interactions curated in HCDT 1.0, we present HCDT 2.0, a comprehensive and standardized resource that expands the scope through multiomics data integration. This update incorporates three-dimensional interactions including drug-gene, drug-RNA and drug-pathway interactions. The current version contains 1,284,353 curated interactions: 1,224,774 drug-gene pairs (678,564 drugs × 5,692 genes), 11,770 drug-RNA mappings (316 drugs × 6,430 RNAs), and 47,809 drug-pathway links (6,290 drugs × 3,143 pathways), alongside 16,317 drug-disease associations. To enhance biological interpretability, we further integrated pathway-gene and RNA-gene regulatory relationships. In addition, we integrated 38,653 negative DTIs covering 26,989 drugs and 1,575 genes. This integrative framework not only addresses critical gaps in cross-scale data representation but also establishes a robust foundation for systems pharmacology applications, including drug repurposing, adverse event prediction, and precision oncology strategies.