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Inhibition of neutral endopeptidase in human fibroblasts homogenates using glutaryl-Ala-Ala-Phe-4-methoxy-2-naphtylamide as substrate after 1 hrs by fluorimetric assay

PubChem AID
620439
Protein Target
Primary Citation
Structure-based design of dipeptide derivatives for the human neutral endopeptidase [PMID: 21937235]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2012-04-30
  • Modify:
    2022-08-30
Description
This bioassay record (AID 620439) reports results from the above primary citation.

1 Description

Title: Structure-based design of dipeptide derivatives for the human neutral endopeptidase.

Abstract: Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC(50) values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases.

2 Comment

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

Journal: Bioorg Med Chem

Year: 2011

Volume: 19

Issue: 20

First Page: 5935

Last Page: 5947

DOI: 10.1016/j.bmc.2011.08.064

Target ChEMBL ID: CHEMBL1944

ChEMBL Target Name: Neprilysin

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

Protein Target

8 Identity

8.1 BioAssay Name

Inhibition of neutral endopeptidase in human fibroblasts homogenates using glutaryl-Ala-Ala-Phe-4-methoxy-2-naphtylamide as substrate after 1 hrs by fluorimetric assay

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2012-04-30

8.7 Modify Date

Version 1.1
Version 2.1
Version 2.2
Version 3.1
Version 3.2
Version 4.1
Version 4.2
Version 4.3
Version 4.4
Version 4.5
Version 5.1
Version 6.1
2022-08-30 (currently shown)

8.8 Status

Live

9 BioAssay Annotations

Assay Type
Binding
Assay Organism

10 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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