2. Academic Validation
  3. Identification of NQO2 As a Protein Target in Small Molecule Modulation of Hepatocellular Function

Identification of NQO2 As a Protein Target in Small Molecule Modulation of Hepatocellular Function

  • ACS Chem Biol. 2021 Sep 17;16(9):1770-1778. doi: 10.1021/acschembio.1c00503.
Arnout G Schepers 1 2,  Jing Shan 1,  Andrew G Cox 3 4,  Ada Huang 1,  Helen Evans 1,  Chad Walesky 3,  Heather E Fleming 1,  Wolfram Goessling 3 5 6 7 8 9,  Sangeeta N Bhatia 1 8 9 10 11 12 13
Affiliations

Affiliations

  • 1 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 2 Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
  • 3 Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 4 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • 5 Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, United States.
  • 6 Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.
  • 7 Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
  • 8 Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 9 Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02139, United States.
  • 10 Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 11 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 12 Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, United States.
  • 13 Wyss Institute at Harvard, Boston, Massachusetts 02115, United States.
PMID: 34427427 DOI: 10.1021/acschembio.1c00503
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12346
    98.94%, Hepatocyte Function Enhancer