An official website of the United States government

Inhibition of C-terminal domain of human sEH-H assessed as reduction in fluorescent naphthalene aldehyde formation using PHOME as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every minute for 45 mins by fluorescence based analysis

PubChem AID
1870507
Primary Citation
Designing a Small Fluorescent Inhibitor to Investigate Soluble Epoxide Hydrolase Engagement in Living Cells [PMID: 35859883]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
1.1
Status
Live
Dates
  • Deposit:
    2023-06-29
  • Modify:
    2023-06-29
Description
This bioassay record (AID 1870507) reports results from the above primary citation. Additional data from the same publication are reported in a total of 11 BioAssay records in PubChem.

1 Description

Title: Designing a Small Fluorescent Inhibitor to Investigate Soluble Epoxide Hydrolase Engagement in Living Cells.

Abstract: Soluble epoxide hydrolase (sEH) is a promising target for a number of inflammation-related diseases. In addition, inhibition of sEH has been shown to reduce neuroinflammation, which plays a critical role in the development of central nervous system (CNS) diseases such as Alzheimer's disease. In this study, we present the rational design of a small fluorescent sEH inhibitor. Starting from the clinical candidate GSK2256294A, we replaced the triazine moiety with the 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) fluorophore. The resulting fluorescent sEH inhibitor displayed excellent potency in an in vitro enzyme activity assay (IC50 < 2 nM). The developed inhibitor is applicable in a NanoBRET-based assay system suitable for studying sEH target engagement in living cells. Furthermore, the inhibitor can be used to visualize sEH in sEH-transfected HEK293 cells and in primary mouse astrocytes by fluorescence microscopy.

2 Comment

Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: ACS Med Chem Lett

Year: 2022

Volume: 13

Issue: 7.0

First Page: 1062

Last Page: 1067

DOI: 10.1021/acsmedchemlett.2c00073

Target ChEMBL ID: CHEMBL2409

ChEMBL Target Name: Epoxide hydratase

ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain

Relationship Type: D - Direct protein target assigned

Confidence: Direct single protein target assigned

3 Result Definitions

4 Data Table

5 Target

8 Identity

8.1 BioAssay Name

Inhibition of C-terminal domain of human sEH-H assessed as reduction in fluorescent naphthalene aldehyde formation using PHOME as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every minute for 45 mins by fluorescence based analysis

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2023-06-29

8.7 Modify Date

Version 1.1
2023-06-29 (currently shown)

8.8 Status

Live

9 Same-Publication BioAssays

10 BioAssay Annotations

Assay Type
Binding
Assay Organism

11 Information Sources

  1. PubChem
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
CONTENTS