VARIDT 4.0: distribution variability of drug transporters

The multilevel distribution variability of drug transporters-from tissues to cells and organelles-is critical for understanding drug response, drug-drug interactions, and multidrug resistance. The absorption, dispersion, metabolism, and excretion properties of drugs are codetermined by these multilevel distribution patterns, including tissue-specific expression, cellular heterogeneity, and subcellular localization. However, a public database that systematically integrates these crucial data of drug transporter distribution variability has been lacking. Therefore, in this major update, VARIDT 4.0 was developed to provide a comprehensive resource, incorporating 25 797 tissue-level expression profiles, 451 830 cell-level expression records, and 1034 subcellular localization entries. Additionally, the foundational modules on general, structural, and regulatory variability were extensively updated. This multilevel variability data is highly relevant to the transport of 889 approved and 221 clinical trial drugs, as well as 689 endogenous metabolites, implicated in the treatment of 558 diseases. Furthermore, by integrating these new distribution layers with its existing data, VARIDT 4.0 now enables comprehensive consideration of how a transporter's function is modulated by its specific spatiotemporal context. Overall, VARIDT 4.0 is expected to be a valuable data repository for system pharmacology, serving as an essential complement to existing pharmaceutical databases, and is freely accessible without login at https://idrblab.org/varidt/.