Application of a Rat Liver Drug Bioactivation Transcriptional Response Assay Early in Drug Development That Informs Chemically Reactive Metabolite Formation and Potential for Drug-induced Liver Injury [PDF]
Toxicological Sciences, 2020 Abstract Drug-induced liver injury is a major reason for drug candidate attrition from development, denied commercialization, market withdrawal, and restricted prescribing of pharmaceuticals. The metabolic bioactivation of drugs to chemically reactive metabolites (CRMs) contribute to liver-associated adverse drug reactions in humans that
James J Monroe +17 more
openalex +4 more sources
Toxicology and Applied Pharmacology, 2022 Drug-induced liver injury (DILI) and cardiotoxicity (DICT) are major adverse effects triggered by many clinically important drugs. To provide an alternative to in vivo toxicity testing, the U.S. Tox21 consortium has screened a collection of ∼10K compounds, including drugs in clinical use, against >70 cell-based assays in a quantitative high-throughput ...
Lin Ye +10 more
openalex +4 more sources
PLOS ONE, 2021 Drug-induced liver injury (DILI) is one of major causes of discontinuing drug development and withdrawing drugs from the market. In this study, we investigated chemical properties associated with DILI using in silico methods, to identify a physicochemical property useful for DILI screening at the early stages of drug development.
Yuki Shimizu +6 more
openalex +6 more sources
Prediction and mechanistic analysis of drug-induced liver injury (DILI) based on chemical structure [PDF]
Biology Direct, 2021 Background Drug-induced liver injury (DILI) is a major safety concern characterized by a complex and diverse pathogenesis. In order to identify DILI early in drug development, a better understanding of the injury and models with better predictivity are ...
Anika Liu +7 more
doaj +2 more sources
Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug‐induced liver injury [PDF]
Liver International, 2013 AbstractBackground & AimsSeveral pharmaceutical compounds have been shown to exert inhibitory effects on the bile salt export pump (BSEP) encoded by the ABCB11 gene. We analysed the combined effect on drug‐induced liver injury (DILI) development of the ABCB11 1331T>C polymorphism and the presence of specific chemical moieties, with known BSEP ...
Eugenia Ulzurrun +12 more
openalex +6 more sources
Development on Animal Models for Drug/Chemical Induced Liver Injury
Biomedical and Pharmacology Journal, 2023 In the human body, the largest gland is the liver and does a lot of essential work of the body. Liver damage is the cause of mortality and increasing day by day. Liver disease is caused by multiple factors, such as an autoimmune condition, toxic chemical exposure, viral infection, and dietary factors.
D. S. Bhatia +3 more
openalex +2 more sources
Characterisation of the NRF2 transcriptional network and its response to chemical insult in primary human hepatocytes: implications for prediction of drug-induced liver injury [PDF]
Archives of Toxicology, 2018 The transcription factor NRF2, governed by its repressor KEAP1, protects cells against oxidative stress. There is interest in modelling the NRF2 response to improve the prediction of clinical toxicities such as drug-induced liver injury (DILI). However, very little is known about the makeup of the NRF2 transcriptional network and its response to ...
Ian M. Copple +15 more
openalex +5 more sources
Definition of the Chemical and Immunological Signals Involved in Drug-Induced Liver Injury
Chemical Research in Toxicology, 2019 Idiosyncratic drug-induced liver injury (iDILI), which is rare and often recognized only late in drug development, poses a major public health concern and impediment to drug development due to its high rate of morbidity and mortality. The mechanisms of DILI are not completely understood; both non-immune- and immune-mediated mechanisms have been ...
Serat-E Ali +3 more
openalex +4 more sources
pDILI_v1: A Web-Based Machine Learning Tool for Predicting Drug-Induced Liver Injury (DILI) Integrating Chemical Space Analysis and Molecular Fingerprints. [PDF]
ACS OmegaAmin SA, Kar S, Piotto S.
europepmc +3 more sources
Advanced human liver models for the assessment of drug-induced liver injury [PDF]
Organoid, 2022 Drug safety issues continue to occur even with drugs that are approved after the completion of clinical studies. Drug-induced liver injury (DILI) is a major obstacle to drug development, because the liver is the primary site of drug metabolism, and ...
Seon Ju Mun +3 more
doaj +1 more source