VARIDT 3.0: the phenotypic and regulatory variability of drug transporter

Author:

Yin Jiayi12,Chen Zhen1,You Nanxin1,Li Fengcheng13,Zhang Hanyu1ORCID,Xue Jia1,Ma Hui1,Zhao Qingwei1,Yu Lushan1,Zeng Su1ORCID,Zhu Feng12ORCID

Affiliation:

1. College of Pharmaceutical Sciences, Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University , Hangzhou  310058 , China

2. Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare , Hangzhou  330110 , China

3. The Children's Hospital, Zhejiang University School of Medicine, Zhejiang University , Hangzhou  310052 , China

Abstract

Abstract The phenotypic and regulatory variability of drug transporter (DT) are vital for the understanding of drug responses, drug-drug interactions, multidrug resistances, and so on. The ADME property of a drug is collectively determined by multiple types of variability, such as: microbiota influence (MBI), transcriptional regulation (TSR), epigenetics regulation (EGR), exogenous modulation (EGM) and post-translational modification (PTM). However, no database has yet been available to comprehensively describe these valuable variabilities of DTs. In this study, a major update of VARIDT was therefore conducted, which gave 2072 MBIs, 10 610 TSRs, 46 748 EGRs, 12 209 EGMs and 10 255 PTMs. These variability data were closely related to the transportation of 585 approved and 301 clinical trial drugs for treating 572 diseases. Moreover, the majority of the DTs in this database were found with multiple variabilities, which allowed a collective consideration in determining the ADME properties of a drug. All in all, VARIDT 3.0 is expected to be a popular data repository that could become an essential complement to existing pharmaceutical databases, and is freely accessible without any login requirement at: https://idrblab.org/varidt/.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Zhejiang Province

National Key R&D Program of China

Leading Talent of the ‘Ten Thousand Plan’ National High-Level Talents Special Support Plan of China

The Double Top-Class Universities

Fundamental Research Funds for Central Universities

Key R&D Program of Zhejiang Province

Westlake Laboratory (Westlake Laboratory of Life Science & Biomedicine); Alibaba Cloud; Information Technology Center of Zhejiang University

Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare

Publisher

Oxford University Press (OUP)

Subject

Genetics

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