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
- Deposit:2012-04-30
- Modify:2022-08-30
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.
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
- PubChem
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