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
-
- Interleukin-6/genetics
- Structure-Activity Relationship
- Biomarkers/metabolism*
- Humans
- Signal Transduction
- Hepatocytes/metabolism*
- Quinone Reductases/antagonists & inhibitors*
- Zebrafish
- Molecular Docking Simulation
- High-Throughput Screening Assays
- Animals
- Liver
- STAT3 Transcription Factor/genetics
- Enzyme Inhibitors/chemistry*
- Enzyme Inhibitors/metabolism
- Tumor Necrosis Factors/genetics
- Gene Expression Regulation/drug effects
- Protein Binding
- 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