PUBLICATION
Identification of NQO2 As a Protein Target in Small Molecule Modulation of Hepatocellular Function
- Authors
- Schepers, A.G., Shan, J., Cox, A.G., Huang, A., Evans, H., Walesky, C., Fleming, H.E., Goessling, W., Bhatia, S.N.
- ID
- ZDB-PUB-210825-5
- Date
- 2021
- Source
- ACS Chemical Biology 16(9): 1770-1778 (Journal)
- Registered Authors
- Goessling, Wolfram
- Keywords
- none
- MeSH Terms
-
- Animals
- Biomarkers/metabolism*
- Enzyme Inhibitors/chemistry*
- Enzyme Inhibitors/metabolism
- Gene Expression Regulation/drug effects
- Hepatocytes/metabolism*
- High-Throughput Screening Assays
- Humans
- Interleukin-6/genetics
- Liver
- Molecular Docking Simulation
- Protein Binding
- Quinone Reductases/antagonists & inhibitors*
- STAT3 Transcription Factor/genetics
- Signal Transduction
- Structure-Activity Relationship
- Tumor Necrosis Factors/genetics
- Zebrafish
- PubMed
- 34427427 Full text @ ACS Chem. Biol.
Citation
Schepers, A.G., Shan, J., Cox, A.G., Huang, A., Evans, H., Walesky, C., Fleming, H.E., Goessling, W., Bhatia, S.N. (2021) Identification of NQO2 As a Protein Target in Small Molecule Modulation of Hepatocellular Function. ACS Chemical Biology. 16(9):1770-1778.
Abstract
The utility of in vitro human disease models is mainly dependent on the availability and functional maturity of tissue-specific cell types. We have previously screened for and identified small molecules that can enhance hepatocyte function in vitro. Here, we characterize the functional effects of one of the hits, FH1, on primary human hepatocytes in vitro, and also in vivo on primary hepatocytes in a zebrafish model. Furthermore, we conducted an analogue screen to establish the structure-activity relationship of FH1. We performed affinity-purification proteomics that identified NQO2 to be a potential binding target for this small molecule, revealing a possible link between inflammatory signaling and hepatocellular function in zebrafish and human hepatocyte model systems.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping