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Inhibition of microsomal epoxide hydrolase (unknown origin) expressed in baculovirus system using CMNMC substrate by fluorescence based assay

PubChem AID
1373464
Protein Target
Primary Citation
Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase [PMID: 29366648]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
1.1
Status
Live
Dates
  • Deposit:
    2020-06-18
  • Modify:
    2020-06-18
Description
This bioassay record (AID 1373464) reports results from the above primary citation. Additional data from the same publication are reported in a total of 25 BioAssay records in PubChem.

1 Description

Title: Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.

Abstract: Multi-target inhibitors have become increasing popular as a means to leverage the advantages of poly-pharmacology while simplifying drug delivery. Here, we describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), two targets known to synergize when treating inflammatory and neuropathic pain. The structure activity relationship (SAR) study described herein initially started with t-TUCB (trans-4-[4-(3-trifluoromethoxyphenyl-l-ureido)-cyclohexyloxy]-benzoic acid), a potent sEH inhibitor that was previously shown to weakly inhibit FAAH. Inhibitors with a 6-fold increase of FAAH potency while maintaining high sEH potency were developed by optimization. Interestingly, compared to most FAAH inhibitors that inhibit through time-dependent covalent modification, t-TUCB and related compounds appear to inhibit FAAH through a time-independent, competitive mechanism. These inhibitors are selective for FAAH over other serine hydrolases. In addition, FAAH inhibition by t-TUCB appears to be higher in human FAAH over other species; however, the new dual sEH/FAAH inhibitors have improved cross-species potency. These dual inhibitors may be useful for future studies in understanding the therapeutic application of dual sEH/FAAH inhibition.

2 Comment

Journal: Bioorg Med Chem Lett

Year: 2018

Volume: 28

Issue: 4

First Page: 762

Last Page: 768

DOI: 10.1016/j.bmcl.2018.01.003

Target ChEMBL ID: CHEMBL1968

ChEMBL Target Name: Epoxide hydrolase 1

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 microsomal epoxide hydrolase (unknown origin) expressed in baculovirus system using CMNMC substrate by fluorescence based assay

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2020-06-18

8.7 Modify Date

Version 1.1
2020-06-18 (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
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